EP2303882A2

EP2303882A2 - Azacarboline derivatives, preparation method thereof and therapeutic use of same

Info

Publication number: EP2303882A2
Application number: EP09761932A
Authority: EP
Inventors: Christopher Arendt; Didier Babin; Olivier Bedel; Thierry Gouyon; Mikhail Levit; Serge Mignani; Neil Moorcroft; David Papin; Ronghua Li
Original assignee: Sanofi Aventis France
Current assignee: Sanofi SA
Priority date: 2008-06-12
Filing date: 2009-06-11
Publication date: 2011-04-06
Also published as: AU2009259114B2; CA2725093A1; AU2009259114A1; US20110178053A1; EA201170002A1; CR11814A; IL209840A0; PE20110122A1; EA018945B1; CN102124007A; ECSP10010670A; BRPI0915204A2; MX2010013699A; DOP2010000366A; JP2011522867A; WO2009150381A2; ZA201008387B; TW201002711A; MA32460B1; WO2009150381A3

Abstract

The invention relates to novel azacarbolines having formula (I), wherein R3, R4 independently represent H, hal, CF₃, substituted oxy, optionally substituted alkoxy, optionally substituted amino, substituted carbonyl, optionally substituted carboxyl, optionally substituted amide, sulphur, such as optionally substituted sulphides, sulphoxides or sulphones, linear, branched or cyclic C₁-C₁₀ alkyl optionally comprising an optionally substituted heteroatom, optionally substituted linear, branched or cyclic C₂-C₇ alkenyl, optionally substituted linear or branched C₂-C₆ alkynyl, optionally substituted aryl or heteroaryl, optionally substituted heterocycloalkyl, R6 represents heteroaryl, C(O)NR1aR1b, heterocycloalkyl or -C(O)heterocycloalkyl, all of which may be optionally substituted; in the form of a base or an acid addition salt. The invention also relates to the therapeutic use of said azacarbolines for the treatment of cancer and to synthesis methods.

Description

AZACARBOLINE DERIVATIVES, THEIR PREPARATION AND THEIR USE

THERAPEUTIC

The present invention relates to α-aza-β-carboline derivatives, to their preparation and to their therapeutic application.

Α-aza-β-carbolines are defined by derivatives of 1,7 diaza carbazole or 8-aza-β-carboline; in official nomenclature the name of this tricyclic unit is 9H-pyrrolo [2,3-b: 5,4-c '] dipyridine.

The present invention relates to compounds acting on protein kinases such as for example: CHK1, CDK1, CDK2, dyrk2, Flt3, GSK3 beta, MNK2, PDGFR beta, PI3K, PIM1, PIM2, PIM3, PLK, TrkB, all of which are involved in the cancer development. More particularly, the present invention relates to compounds acting on a target called Pim involved in the development of cancers.

Pim kinases, encompassing Pim-1, Pim-2 and Pim-3, form a distinct family of serine / threonine kinases, and play a functional role in cell growth, differentiation and apoptosis. One of the mechanisms by which Pim kinases can increase cancer cell survival and promote cancer progression is through the modulation of ADB activity, a key regulator of apoptosis. Pim kinases are highly homologous to each other and display similar oncogenic behavior.

Clinical reports highlight the importance of the role of PIM kinases in the development of human cancers.

Pim kinases, particularly Pim-1 and Pim-2, have been found to be abnormally expressed in a large number of hematological malignancies. Amson et al. report the overexpression of Pim-1 in acute myeloid leukemia and acute lymphoid leukemia, and that overexpression of Pim-1 appears to result from inappropriate activation in various leukemias (Proc Natl Acad ScL, Vol 86, 8857-8861 (1989)). Studies have demonstrated overexpression of Pim-1 in primary and metastatic CNS lymphoma, an aggressive form of non-Hodgkin lymphoma (Rubenstein et al., Blood, Vol 107, 9, 3716-3723 (2006)). ). Höttmann et al. have also found overexpression of Pim-2 in B-cell chronic lymphocytic leukemia and suggest that upregulation of Pim-2 may be associated with a more aggressive course of the disease (Leukemia, 20, 1774- 1782 ( 2006)). Abnormal expression of Pim-1 and Pim-2 has been linked to multiple myeloma (Claudio et al., Blood, v. 100, No. 6, 2175-2186 (2002)).

Hypermutation of Pim-1 has been identified in diffuse large cell lymphoma (Pasqualucci et al., Nature, Vol 412, 2001, pp 341-346 (2001)) and in Hodgkin's lymphoma classical and nodular predominantly lymphocytic (Liso et al., Blood, Vol.108, No. 3, 1013-1020 (2006)).

Numerous studies have also linked abnormal expression of Pim kinases to various non-hematological human cancers (prostate, pancreas, head and neck, etc.) and their presence is often associated with a more aggressive phenotype. For example, both Pim-1 and Pim-2 have been implicated in prostate cancer (Chen et al., Mol Cancer Res, 3 (8) 443-451 (2005)). Valdman et al. have demonstrated upregulation of Pim-1 in patients with prostate carcinoma and in high-grade prostatic intraepithelial neoplasia (precancerous lesions) (The Prostate, (60) 367-371 (2004) ), while Dai et al. suggest that overexpression of Pim-2 in prostate cancer is associated with more aggressive clinical features (The Prostate, 65: 276-286 (2005)). Xie et al. found that 44 kDa Pim-1 (Pim-IL) was significantly upregulated in human prostate tumor specimens, and indicate that Pim-IL has an anti-apoptotic effect on prostate cancer cells in response to chemotherapeutic drugs (Oncogene, 25, 70-78 (2006)).

Pim-2 is linked to the perineural invasion (PNI), during which cancer cells curl around the nerves, which are often found in certain cancers such as cancers of the prostate, pancreas, ducts biliary and head and neck (Ayala et al., Cancer Research, 64, 6082 - 6090 (2004)). According to Li et al., Pim-3 is aberrantly expressed in human and mouse hepatocarcinomas and human pancreatic cancer tissues (Cancer Res 66 (13), 6741-6747 (2006)). Aberrant expression of Pim-3 has also been observed in gastric adenoma and metastatic sites of gastric carcinoma (Zheng et al., J Cancer Res Clin Oncol, 134: 481-488 (2008)).

Together, these reports suggest that Pim kinase inhibitors are useful for the treatment of cancer, including leukemias, lymphomas, myelomas, and various solid tumors, including head and neck cancers, colon cancer, prostate cancer, pancreatic cancer, liver cancer and oral cancer, for example. Since cancer remains a disease for which existing therapies are inadequate, it is clearly necessary to identify new inhibitors of Pim kinases that are effective in the treatment of cancer.

Among the patent applications claiming compounds of the azacarboline class, object of our invention, mention may be made of the following documents:

The patent application WO 2007/044779 describes α-aza-β-carbolines of the following general formula, partially restricted, with respect to the application as published:

In which - Z5, Z4 and Z3 can represent C and

Z and Z2 may also represent C,

Zl can finally represent C or N and

R 2 can represent a carbon bond or an alkylene radical each of which may be substituted by numerous possibilities, among which are heteroaryloxy, heteroaryl (C 1 -C 5) alkyl, heteroaryls and heterobicycloaryls.

The preparation process as well as all the examples of this application are limited to derivatives substituted in position 2 and 8 and optionally in position 5.

The patent EP 1 209 158 claims compounds of the following formula:

Where B6, B7, B8, B9 may be C or N, and R7 is never heteroaryl. The activity of the compounds of this invention is particularly directed to the treatment of cardiac problems.

The present invention relates to compounds of the following general formula:

in which

- R3, R4 can be independently of one another:

1. H;

2. halogen;

3. CF ₃ ; 4. substituted oxy;

5. optionally substituted alkoxy;

6. optionally substituted amino;

7. substituted carbonyl;

8. optionally substituted carboxyl;

9. optionally substituted amide;

10. Sulfur at various oxidation levels (II or IV or VI) such as sulfides, sulfoxides or optionally substituted sulfones;

Linear, branched or cyclic CpCio alkyl optionally comprising an optionally substituted heteroatom;

12. C ₂ -C 7 linear, branched or cyclic optionally substituted alkenyl;

13. C ₂ -C 6 alkynyl linear or branched optionally substituted;

Aryl or optionally substituted heteroaryl;

15. optionally substituted heterocycloalkyl;

- R6 is a heteroaryl (5- or 6-membered with 1 to 4 heteroatom selected from N, S or O) linked to the azacarboline moiety either by a C or an N belonging to R6, R6 being optionally substituted; R6 may also represent C (O) NRIaRIb or an optionally substituted heterocycloalkyl or - C (O) optionally substituted heterocycloalkyl, such that RIa and RIb may be independently of one another:

1. H;

2. Cl-ClO alkyl linear or branched or cyclic (C3-C7) optionally mono or di substituted;

3. C2-C6 linear or branched alkenyl optionally mono or di substituted;

4. C2-C6 linear or branched alkynyl optionally mono or di substituted;

5. aryl optionally mono or di substituted;

6. optionally mono or di substituted heteroaryl;

7. optionally mono or di substituted benzyl;

8. COalkyl optionally mono or di substituted;

9. optionally mono or di substituted Caryl;

10. optionally mono or di substituted heteroaryl;

11. C02alkyl optionally mono or di substituted;

12. C02aryl optionally mono or di substituted;

13. CO2heteroaryl optionally mono or di substituted;

14. CONH2,

15. CONHalkyl optionally mono or di substituted;

16. CONHaryl optionally mono or di substituted;

17. CONHheteroaryl optionally mono or di substituted;

18. CON (alkyl) 2 optionally mono or di substituted;

19. CON (aryl) 2 optionally mono or di substituted;

20. CON (heteroaryl) 2 optionally mono or di substituted; said products of formula (I) being in the form of a base or an addition salt with an acid.

The invention more specifically relates to compounds for which:

- R3, R4 can be independently of one another:

1. H;

2 F ;

3. Cl;

4. Br;

5. i;

6. CF ₃ ;

7. OR2a;

8. NRIaRIb;

9. COR2a;

10. CO ₂ R2a; 11. CO (NRIaRIb);

12. SR2a;

13. SOR2a;

14. SO ₂ R2a;

15. CpCio linear or branched or cyclic (C ₃ -C ₇ ) alkyl optionally mono- or di or tri substituted by R2a, R2b, R2c;

16. C ₂ -C _O linear or branched or cyclic (C ₃ -C 7) alkenyl optionally mono or di or tri substituted by R2a, R2b, R2c;

17. C2-C6 linear or branched alkynyl optionally mono or di or tri substituted by R2a, R2b, R2c;

18. aryl or heteroaryl optionally mono or di or tri substituted by R2a, R2b, R2c;

19. heterocycloalkyl optionally mono or di or tri substituted by R2a, R2b, R2c;

R 6 is a heteroaryl (5 or 6-membered with 1 to 4 heteroatoms (N, S or O) bonded to the azacarboline unit, either by a C or an N belonging to R 6, R 6 may also represent C (O) NRIaRIb or a heterocycloalkyl or -C (O) heterocycloalkyl, R6 being optionally mono or di or tri substituted by R2a, R2b, R2c wherein R2a, R2b and R2c are as described above or below and in particular in the examples.

It is specified that in the products of formula (I) as defined above or below, the groups R followed by only one number (R3, R4 and R6) are substituents directly linked to the tricyclic unit while the groups R followed by a number and a letter (for example RIa, R2b or R3a) correspond to higher degrees of substitution (for example substituent of R3, R4 or R6) and can not be directly related to the tricyclic unit.

In the substituents mentioned above:

- RIa and RIb can be independently of one another:

1. H;

2. C ₁ -C ₁₀ linear or branched or cyclic (C ₃ -C ₇ ) alkyl, optionally mono- or di-substituted;

3. C ₂ -C 6 linear or branched alkenyl optionally mono or di substituted;

4. C ₂ -C 6 linear or branched alkynyl optionally mono or di substituted;

5. aryl optionally mono or di substituted;

6. optionally mono or di substituted heteroaryl;

7. optionally mono or di substituted benzyl;

8. COalkyl optionally mono or di substituted;

9. optionally mono or di substituted Caryl;

10. optionally mono or di substituted heteroaryl;

11. C _{2 2} alkyl optionally mono or di substituted;

12. C _{2 2} aryl optionally mono or di substituted;

13. Có ₂ heteroaryl optionally mono or di substituted;

14. CONH ₂ ,

15. CONHalkyl optionally mono or di substituted;

16. CONHaryl optionally mono or di substituted;

17. CONHheteroaryl optionally mono or di substituted;

18. CO N (alkyl) ₂ optionally mono or di substituted;

19. C0N (aryl) ₂ optionally mono or di substituted;

20. CON (heteroaryl) ₂ optionally mono or di substituted;

The optional substituents R2a, R2b or R2c are chosen independently of one another from:

1. F;

2. Cl;

3. Br;

4. I;

5. CF ₃ ;

6. Cp -Cio linear or branched alkyl optionally mono or poly substituted;

7. C ₃ -C ₇ cycloalkyl optionally mono or poly substituted; 8. C ₂ -C ₆ alkenyl optionally mono or poly substituted;

9. C ₂ -C ₆ alkynyl optionally mono or poly substituted;

10. OH;

11. Linear or branched, optionally mono or poly substituted O-alkyl (C 1 -C 10);

12. O-cycloalkyl (C ₃ -C ₇ ) optionally mono or poly substituted;

13. O-aryl optionally mono or poly substituted;

14. aryl optionally mono or poly substituted;

15. optionally mono or poly substituted heteroaryl;

16. optionally mono or poly substituted heterocycloalkyl;

17. NH ₂ ;

18. NH- (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl or heterocycloalkyl) each optionally mono or poly substituted group;

19. N (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl) ₂ each group being optionally mono or poly substituted;

20. NH- (aryl or heteroaryl) optionally mono or poly substituted;

21. N (aryl or heteroaryl) ₂ each group being optionally mono or poly substituted;

22. N (aryl or heteroaryl) (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl) each group being optionally mono or poly substituted;

23. NHC (O) R3a;

24. N (C ₁ -C 10 alkyl) C (O) R 3 a;

25. N (R3a) C (O) R3b;

26. NHS (O) ₂ R3a;

27. N (C ₁ -C 10 alkyl) S (O) ₂ R 3 a;

28. N (R3a) S (O) ₂ R3b;

29. CO ₂ R3a;

30. SR3a;

31. SOR3a;

32. SO ₂ R3a; where R3a is as defined in the examples.

The optional substituents of the groups RIa, RIb and R2a, R2b and R2c groups also called R3a, R3b or R3c groups are chosen from:

1. halogen;

2. CF ₃ ;

3. CpCio linear or branched alkyl

4. C ₃ -C ₇ cycloalkyl;

5. C ₂ -C ₆ alkenyl;

6. C ₂ -C ₆ alkynyl;

7. C1-C10 alkylhydroxy

8. CpCio alkoxy

9. CpCio alkylamino

10. OH;

11. linear, branched or cyclic (C ₃ -C ₇ ) -alkyl (C ₁ -C ₁₀ );

12. O-aryl;

13. aryl;

14. heteroaryl;

15. heterocycloalkyl;

16. NH ₂ ;

17. NH (C (C _r Cio) cycloalkyl or (C ₃ -C _7));

18. N (alkyl (C _r Cio) cycloalkyl or (C ₃ -C ₇₎₎ _2;

19. NH- (aryl or heteroaryl);

20. N (aryl or heteroaryl) ₂ ;

21. N (aryl or heteroaryl) (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl);

22. NHC (0) - (alkyl (C _r Cio) cycloalkyl or (C ₃ -C ₇₎ or heterocycloalkyl);

23. NHC (O) - (aryl or heteroaryl);

24. NHS (0) ₂ - (alkyl (C _r Cio) cycloalkyl or (C ₃ -C ₇₎ or heterocycloalkyl); 25. NHS (O) ₂ - (aryl or heteroaryl);

26. CO (Ci-Ci ₀ linear or branched alkyl);

27. CO (Ci-Ci ₀ alkylamino);

28. CO ₂ (Ci-CiO linear or branched alkyl);

29. C (O) NH (Ci-Ci ₀ linear or branched alkyl);

30. C (O) N (Ci-CiO linear or branched alkyl) ₂ ;

31. S (C1-C10 linear or branched alkyl);

32. SO (Ci-CiO linear or branched alkyl);

33. SO ₂ (Ci-CiO linear or branched alkyl)

34. C (O) (heterocycloalkyl).

The present invention relates to all the compounds of the following general formula:

in which

- R3, R4 can be independently of one another: l.H;

2 F ;

3.Cl;

4.Br;

5.1;

6.CF ₃ ;

7.0R2a;

8.NRIaRIb;

9.COR2a;

10. CO ₂ R2a;

11. CO (NRIaRIb);

12. SR2a;

13. SOR 2a;

14. SO ₂ R2a;

15. Cp -Cio linear or branched or cyclic (C3-C7) alkyl optionally mono- or di or tri substituted by R2a, R2b, R2c;

16. C ₂ -C ₆ linear or branched or cyclic (C ₃ -C ₇ ) alkenyl optionally mono or di or tri substituted by R2a, R2b, R2c;

17. C ₂ -C ₆ linear or branched alkynyl optionally mono or di or tri substituted by R2a, R2b, R2c;

18. aryl or heteroaryl optionally mono or di or tri substituted by R2a, R2b, R2c

19. heterocycloalkyl optionally mono or di or tri substituted by R2a, R2b, R2c

- R6 is a heteroaryl (5 or 6-membered with 1 to 4 heteroatom N, S or O) linked to the azacarboline unit or by a C or N belonging to R6, R6 may also represent C (O) NRIaRIb or an optionally substituted heterocycloalkyl or -C (O) optionally substituted heterocycloalkyl; R6 being optionally mono or di or tri substituted by R2a, R2b, R2c; wherein:

-RIa and RIb can be independently of each other: 1. H; 2. CpCio linear or branched or cyclic (C3-C7) alkyl optionally mono or di substituted by R2a R2b;

3. C ₂ -C 6 linear or branched alkenyl optionally mono or di substituted with R2a R2b;

4. C ₂ -C 6 linear or branched alkynyl optionally mono or di substituted with R2a R2b;

Aryl optionally mono or di substituted with R2a R2b;

6. heteroaryl optionally mono or di substituted with R2a R2b;

Benzyl optionally mono or di substituted with R2a R2b;

8. COalkyl optionally mono or di substituted with R2a R2b;

9. Caryl optionally mono or di substituted with R2a R2b;

10.Heteroaryl optionally mono or di substituted with R2a R2b;

11. Cθ ₂ alkyl optionally mono or di substituted with R2a R2b;

12. Cθ ₂ aryl optionally mono or di substituted with R2a R2b;

13. C _{2 2} heteroaryl optionally mono or di substituted with R2a R2b;

14. CONH ₂ ,

15. CONHalkyl optionally mono or di substituted with R2a R2b;

16. CONHaryl optionally mono or di substituted with R2a R2b;

17. CONHheteroaryl optionally mono or di substituted with R2a R2b;

18. C0N (alkyl) ₂ optionally mono or di substituted with R2a R2b;

19. C0N (aryl) ₂ optionally mono or di substituted with R2a R2b;

20. CON (heteroaryl) ₂ optionally mono or di substituted with R2a R2b; wherein R2a, R2b, R2c are independently selected from:

1. F;

2. Cl;

3. Br;

4. I;

5. CF ₃ ;

6. Cp -Cio linear or branched alkyl optionally mono or poly substituted with different R3a;

C3-C7 cycloalkyl optionally mono or poly substituted with different R3a;

8. C ₂ -C 6 alkenyl optionally mono or poly substituted with different R 3a;

9. C ₂ -C 6 alkynyl optionally mono or poly substituted with different R 3a;

10. OH;

11. linear or branched O-alkyl (C 1 -C 10) optionally mono or poly substituted with different R 3a;

12. O-cycloalkyl (C ₃ -C ₇ ) optionally mono or poly substituted with different R 3a;

13. O-aryl optionally mono or poly substituted with different R3a;

Aryl optionally mono or poly substituted with different R3a;

15. heteroaryl optionally mono or poly substituted with different R3a;

16. heterocycloalkyl optionally mono or poly substituted with different R3a;

17. NH ₂ ;

18. NH- (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl or heterocycloalkyl) each optionally mono or poly group substituted with different R 3a;

19. N (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl) ₂ each group being optionally mono or poly substituted with different R 3a;

20. NH- (aryl or heteroaryl) optionally mono or poly substituted with different R3a;

21. N (aryl or heteroaryl) ₂ each group being optionally mono or poly substituted with different R3a;

22. N (aryl or heteroaryl) (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl) each group being optionally mono or poly substituted with different R 3a;

23. NHC (O) R3a;

24. N (C ₁ -C 10 alkyl) C (O) R 3 a;

25. N (R3a) C (O) R3b;

26. NHS (O ₂ ) R3a; 27. N (C ₁ -C 10 alkyl) S (O ₂ ) R 3 a;

28. N (R3a) S (O) ₂ R3b;

29. CO ₂ R3a;

30. SR3a;

31. SOR3a;

32. SO ₂ R3a. in which R3a and R3b are chosen from:

1. halogen;

2. CF ₃ ;

3. CpCio linear or branched alkyl

4. C ₃ -C ₇ cycloalkyl;

5. C ₂ -CO alkenyl;

6. C ₂ -C ₆ alkynyl;

7. CpCio alkylhydroxy

8. CpCio alkoxy

9. CpCio alkylamino

10. OH;

11. linear, branched or cyclic (C ₃ -C ₇ ) -alkyl (C ₁ -C ₁₀ );

12. O-aryl;

13. aryl;

14. heteroaryl;

15. heterocycloalkyl;

16. NH ₂ ;

17. NH (C (C _r Cio) cycloalkyl or (C ₃ -C _7));

18. N (alkyl (C _r Cio) cycloalkyl or (C ₃ -C ₇₎₎ _2;

19. NH- (aryl or heteroaryl);

20. N (aryl or heteroaryl) ₂ ;

21. N (aryl or heteroaryl) (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl);

23. NHC (O) - (aryl or heteroaryl);

24. NHS (0) ₂ - (alkyl (C _r Cio) cycloalkyl or (C ₃ -C ₇₎ or heterocycloalkyl);

25. NHS (O) ₂ - (aryl or heteroaryl);

26. CO (Ci-CiO linear or branched alkyl);

27. CO (Ci-Ci ₀ alkylamino);

28. CO ₂ (Ci-CiO linear or branched alkyl);

29. C (O) NH (Ci-Ci ₀ linear or branched alkyl);

30. C (O) N (Ci-CiO linear or branched alkyl) ₂ ;

31. S (C1-C10 linear or branched alkyl);

32. SO (Ci-Ci ₀ linear or branched alkyl);

33. SO ₂ (Ci-CiO linear or branched alkyl)

34. C (O) (heterocycloalkyl). said products of formula (I) being in the form of a base or an addition salt with an acid.

The present invention thus relates to compounds of the following general formula:

in which

- R3, R4 can be independently of one another:

1. H;

2. halogen;

3. CF ₃ ;

4. substituted oxy;

5. optionally substituted alkoxy;

6. optionally substituted amino;

7. substituted carbonyl;

8. optionally substituted carboxyl;

9. optionally substituted amide;

10. sulfur at different oxidation levels (II or IV or VI) such as sulfide, sulfoxide or optionally substituted sulfone;

12. C ₂ -C 7 linear, branched or cyclic optionally substituted alkenyl;

13. C ₂ -C 6 alkynyl linear or branched optionally substituted;

Aryl or optionally substituted heteroaryl;

- R6 is a heteroaryl (5 or 6-membered with 1 to 4 heteroatom selected from N, S or O) linked to the azacarboline unit either by a C or by an N belonging to R6, R6 being optionally substituted.

The invention more specifically relates to compounds for which:

- R3, R4 can be independently of one another:

1. H;

2 F ;

3. Cl;

4. Br;

5. I;

6. CF ₃ ;

7. OR2a;

8. NRIaRIb;

9. COR2a;

10. CO ₂ R2a;

11. CO (NRIaRIb);

12. SR2a;

13. SOR2a;

14. SO ₂ R2a;

16. C ₂ -C _O linear or branched or cyclic (C ₃ -C ₇ ) alkenyl optionally mono or di or tri substituted by R2a, R2b, R2c;

19. heterocycloalkyl optionally mono or di or tri substituted by R2a, R2b, R2c;

R 6 is a heteroaryl (5 or 6-membered with 1 to 4 heteroatoms (N, S or O) bonded to the azacarboline unit, either by a C or an N belonging to R 6, R 6 being optionally mono or di or tri substituted with R 2a, R 2b; , R2c where R2a, R2b and R2c are as described in the examples.

In the substituents mentioned above:

- RIa and RIb can be independently of one another:

1. H;

3. C ₂ -C 6 linear or branched alkenyl optionally mono or di substituted;

4. C ₂ -C 6 linear or branched alkynyl optionally mono or di substituted; 5. aryl optionally mono or di substituted;

6. optionally mono or di substituted heteroaryl;

7. optionally mono or di substituted benzyl;

8. COalkyl optionally mono or di substituted;

9. optionally mono or di substituted Caryl;

10. optionally mono or di substituted heteroaryl;

11. C0 ₂ optionally mono or di substituted alkyl;

12. C0 ₂ aryl optionally mono or di substituted;

13. Có ₂ heteroaryl optionally mono or di substituted;

14. CONH ₂ ,

15. CONHalkyl optionally mono or di substituted;

16. CONHaryl optionally mono or di substituted;

17. CONHheteroaryl optionally mono or di substituted;

18. CO N (alkyl) ₂ optionally mono or di substituted;

19. C0N (aryl) ₂ optionally mono or di substituted;

20. CON (heteroaryl) ₂ optionally mono or di substituted;

1. F;

2. Cl;

3. Br;

4. I;

5. CF ₃ ;

6. Cp -Cio linear or branched alkyl optionally mono or poly substituted;

7. C ₃ -C ₇ cycloalkyl optionally mono or poly substituted;

8. C ₂ -C _O alkenyl optionally mono or poly substituted;

9. C ₂ -C ₆ alkynyl optionally mono or poly substituted;

10. OH;

12. O-cycloalkyl (C ₃ -C ₇ ) optionally mono or poly substituted;

13. O-aryl optionally mono or poly substituted;

14. aryl optionally mono or poly substituted;

15. optionally mono or poly substituted heteroaryl;

16. optionally mono or poly substituted heterocycloalkyl;

17. NH ₂ ;

20. NH- (aryl or heteroaryl) optionally mono or poly substituted;

23. NHC (O) R3a;

24. N (C ₁ -C 10 alkyl) C (O) R 3 a;

25. NHC (O) - (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl or heterocycloalkyl each group being optionally mono or poly substituted;

26. NC (O) (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl or heterocycloalkyl ₂ each group being optionally mono or poly substituted;

27. NHC (O) - (aryl or heteroaryl) optionally mono or poly substituted;

28. NC (O) (aryl or heteroaryl) ₂ each group being optionally mono or poly substituted;

29. CN (O) (aryl or heteroaryl) (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl or heterocycloalkyl) each group being optionally mono or poly substituted;

30. NHS (O ₂ ) R3a;

31. N (C ₁ -C 10 alkyl) S (O ₂ ) R 3 a; 32. NHS (θ2) - (alkyl (Ci-Cio) cycloalkyl or (C3-C ₇₎ or heterocycloalkyl) each group being optionally mono or poly substituted;

33. NS (θ2) (alkyl (Ci-Cio) cycloalkyl or (C3-C ₇₎ or heterocycloalkyl) 2 group each optionally mono or poly substituted;

34. NHS (O ₂ ) - (aryl or heteroaryl) optionally mono or poly substituted;

35. NS (θ ₂ ) (aryl or heteroaryl) ₂ each group being optionally mono or poly substituted;

36. NS (O ₂₎ (aryl or heteroaryl) (alkyl (Ci-Ci ₀₎ cycloalkyl or (C ₃ -C ₇₎ or heterocycloalkyl) each group being optionally mono or poly substituted;

37. COR3a;

38. CO ₂ R3a;

39. SR3a;

40. SOR3a;

41. SO ₂ R3a; where R3a is as defined in the examples.

1. halogen;

2. CF ₃ ;

3. CpCio linear or branched alkyl

4. C ₃ -C ₇ cycloalkyl;

C2-C6 alkenyl;

6. C ₂ -C ₆ alkynyl;

7. OH;

8. linear, branched or cyclic (C ₃ -C ₇ ) -alkyl (C ₁ -C ₁₀ );

9. O-aryl;

10. aryl;

11. heteroaryl;

12. heterocycloalkyl;

13. NH ₂ ;

14. NH (C (C _r Cio) cycloalkyl or (C ₃ -C _7));

15. N (alkyl (C _r Cio) cycloalkyl or (C ₃ -C ₇₎₎ _2;

16. NH- (aryl or heteroaryl);

17. N (aryl or heteroaryl) ₂ ;

18. N (aryl or heteroaryl) (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl);

19. NHC (O) - (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl or heterocycloalkyl;

20. NC (0) (alkyl (C _r Cio) cycloalkyl or (C ₃ -C ₇₎ or heterocycloalkyl) _2;

21. NHC (O) - (aryl or heteroaryl);

22. NC (O) (aryl or heteroaryl) ₂ ;

23. NC (O) (aryl or heteroaryl) (alkyl (Ci-Ci ₀₎ cycloalkyl or (C ₃ -C ₇₎ or heterocycloalkyl);

24. NHS (0 ₂₎ - (alkyl (C _r Cio) cycloalkyl or (C ₃ -C ₇₎ or heterocycloalkyl);

25. NS (0 ₂₎ (alkyl (C _r Cio) cycloalkyl or (C ₃ -C ₇₎ or heterocycloalkyl) _2;

26. NHS (O ₂ ) - (aryl or heteroaryl);

27. NS (O ₂ ) (aryl or heteroaryl) ₂ ;

28. NS (O ₂₎ (aryl or heteroaryl) (alkyl (Ci-Ci ₀₎ cycloalkyl or (C ₃ -C ₇₎ or heterocycloalkyl);

29. CO (Ci-CiO linear or branched alkyl);

30. CO ₂ (Ci-CiO linear or branched alkyl);

31. C (O) NH (Ci-Ci ₀ linear or branched alkyl);

32. C (O) N (Ci-CiO linear or branched alkyl) ₂ ;

33. S (Ci-CiO linear or branched alkyl);

34. SO (Ci-Ci ₀ linear or branched alkyl);

35. SO ₂ (Ci-CiO linear or branched alkyl).

The group R 6 is a 5- or 6-membered heteroaryl preferably chosen from pyridine, pyrazole, imidazole or triazole groups optionally substituted with R 2a. The present invention relates to all the compounds of the following general formula:

in which

- R3, R4 can be independently of one another:

1. H;

2 F ;

3. Cl;

4. Br;

5. I;

6. CF ₃ ;

7. OR2a;

8. NRIaRIb;

9. COR2a;

10. CO ₂ R2a;

11. CO (NRIaRIb);

12. SR2a;

13. SOR2a;

14. SO ₂ R2a;

17. C ₂ -C ₀ alkynyl linear or branched optionally mono- or di or tri substituted by R2a, R2b, R2c;

19. heterocycloalkyl optionally mono or di or tri substituted by R2a, R2b, R2c;

- R6 is a heteroaryl (5 or 6-membered with 1 to 4 N, S or O heteroatom) linked to the azacarboline unit or by a C or N belonging to R6, R6 being optionally mono or di or tri substituted by R2a, R2b, R2c; in which RIa and RIb can be independently of one another:

1. H;

2. CpCio linear or branched or cyclic (C ₃ -C ₇ ) alkyl optionally mono- or di substituted by R2a R2b;

3. C ₂ -C _O linear or branched alkenyl optionally mono or di substituted by R2a R2b;

4. C ₂ -C ₀ alkynyl linear or branched optionally mono or di substituted by R2a R2b;

Aryl optionally mono or di substituted with R2a R2b;

6. heteroaryl optionally mono or di substituted with R2a R2b;

Benzyl optionally mono or di substituted with R2a R2b;

8. COalkyl optionally mono or di substituted with R2a R2b;

9. Caryl optionally mono or di substituted with R2a R2b;

10.Heteroaryl optionally mono or di substituted with R2a R2b;

11. C0 ₂ alkyl optionally mono or di substituted with R2a R2b;

12. C0 ₂ aryl optionally mono or di substituted with R2a R2b; 13. C _{2 2} heteroaryl optionally mono or di substituted with R2a R2b;

14. CONH ₂ ,

15. CONHalkyl optionally mono or di substituted with R2a R2b;

16. CONHaryl optionally mono or di substituted with R2a R2b;

17. CONHheteroaryl optionally mono or di substituted with R2a R2b;

18. C0N (alkyl) ₂ optionally mono or di substituted with R2a R2b;

19. C0N (aryl) ₂ optionally mono or di substituted with R2a R2b;

20. CON (heteroaryl) ₂ optionally mono or di substituted with R2a R2b wherein R2a, R2b, R2c are independently selected from:

1. F;

2. Cl;

3. Br;

4. I;

5. CF ₃ ;

C3-C7 cycloalkyl optionally mono or poly substituted with different R3a;

8. C ₂ -C 6 alkenyl optionally mono or poly substituted with different R 3a;

9. C ₂ -C 6 alkynyl optionally mono or poly substituted with different R 3a;

10. OH;

13. O-aryl optionally mono or poly substituted with different R3a;

Aryl optionally mono or poly substituted with different R3a;

15. heteroaryl optionally mono or poly substituted with different R3a;

16. heterocycloalkyl optionally mono or poly substituted with different R3a;

17. NH ₂ ;

23. NHC (O) R3a;

24. N (C ₁ -C 10 alkyl) C (O) R 3 a;

25. NHC (O) - (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl or heterocycloalkyl) each group optionally being mono or poly substituted with different R 3a;

26. NC (O) (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl or heterocycloalkyl ₂ each group being optionally mono or poly substituted with different R 3a;

27. NHC (O) - (aryl or heteroaryl) optionally mono or poly substituted with different R3a;

28. NC (O) (aryl or heteroaryl) ₂ each group being optionally mono or poly substituted with different R3a;

29. NC (O) (aryl or heteroaryl) (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl or heterocycloalkyl) each group being optionally mono or poly substituted with different R 3a;

30. NHS (O ₂ ) R3a;

31. N (C ₁ -C 10 alkyl) S (O ₂ ) R 3 a;

32. NHS (O ₂ ) - (C ₁ -C ₁₀ alkyl) or (C ₃ -C ₇ ) cycloalkyl or heterocycloalkyl) each group being optionally mono or poly substituted with different R 3a;

33. NS (0 ₂₎ (alkyl (Ci-Cio) cycloalkyl or (C ₃ -C ₇₎ heterocycloalkyl or) ₂ group each optionally mono or poly substituted with various R3a;

34. NHS (O ₂ ) - (aryl or heteroaryl) optionally mono or poly substituted with different R3a; 35. NS (θ ₂ ) (aryl or heteroaryl) ₂ each group being optionally mono or poly substituted with different R3a;

36. NS (θ2) (aryl or heteroaryl) (C 1 -C 10 alkyl) or C ₃ -C ₇ cycloalkyl or heterocycloalkyl) each group being optionally mono or poly substituted by different R 3a; COR3a;

37. CO ₂ R3a;

38. SR3a;

39. S0R3a;

40. SO ₂ R3a. in which R3a is selected from:

1. halogen;

2. CF ₃ ;

3. CpCio linear or branched alkyl

4. C ₃ -C ₇ cycloalkyl;

5. C ₂ -CO alkenyl;

6. C ₂ -CO alkynyl;

7. OH;

8. linear, branched or cyclic (C ₃ -C ₇ ) -alkyl (C ₁ -C ₁₀ );

9. O-aryl;

10. aryl;

11. heteroaryl;

12. heterocycloalkyl;

13. NH ₂ ;

14. NH (C (C _r Cio) cycloalkyl or (C ₃ -C _7));

15. N (alkyl (C _r Cio) cycloalkyl or (C ₃ -C ₇₎₎ _2;

16. NH- (aryl or heteroaryl);

17. N (aryl or heteroaryl) ₂ ;

18. N (aryl or heteroaryl) (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl);

19. NHC (0) - (alkyl (C _r Cio) cycloalkyl or (C ₃ -C ₇₎ or heterocycloalkyl);

21. NHC (O) - (aryl or heteroaryl);

22. NC (O) (aryl or heteroaryl) ₂ ;

23. NC (O) (aryl or heteroaryl) (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl or heterocycloalkyl;

26. NHS (O ₂ ) - (aryl or heteroaryl);

27. NS (O ₂ ) (aryl or heteroaryl) ₂ ;

28. NS (O ₂ ) (aryl or heteroaryl) (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl or heterocycloalkyl;

29. CO (Ci-CiO linear or branched alkyl);

30. CO ₂ (Ci-Ci ₀ linear or branched alkyl);

31. C (O) NH (Ci-Ci ₀ linear or branched alkyl);

32. C (O) N (Ci-CiO linear or branched alkyl) ₂ ;

33. S (Ci-Ci ₀ linear or branched alkyl);

34. SO (Ci-CiO linear or branched alkyl);

35. SO ₂ (Ci-Ci ₀ linear or branched alkyl).

In the context of the present invention the positions 2 and 8 should not be substituted contrary to the documents of the prior art.

Alkyl (Ci-Cio) or Ci-Cio alkyl means all carbon chains of 1 to 10 carbons, saturated, linear or branched.

Aryl means phenyl or naphthyl. Cycloalkyl (C3-C ₇₎ means any non-aromatic rings consisting solely of carbon atoms, including cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane; but may also carry an unsaturation, for example cyclopentene, cyclohexene, cycloheptene ...

CpCio alkylhydroxy means all carbon chains of 1 to 10 carbons, saturated, linear or branched bearing at least one hydroxy group (OH).

CpCio alkoxy means all carbon chains of 1 to 10 carbons, saturated, linear or branched in which there is at least one ether function (C-O-C).

CpCio alkylamino means all carbon chains of 1 to 10 carbons, saturated, linear or branched in which there is at least one amine function (primary, secondary or tertiary).

Heteroaryl means any 5- or 6- or 7-membered aromatic mono-ring having at least one heteroatom (N, O, S), especially pyridine, pyrimidine, imidazole, pyrazole, triazole, thiophene, furan, thiazole, oxazole, and the like. that the bicyclic aromatic systems possessing at least one heteroatom (N, O, S) in particular indole, benzimidazole, azaindole, benzofuran, benzothiophene, quinoline, etc.

Heterocycloalkyl means all monocycles and bicycles (spiro or non-aromatic) having at least one heteroatom (N, O, S) with or without unsaturation, in particular: morpholine, piperazine, 4-methyl piperazine, 4-methylsulfonyl piperazine, piperidine, pyrolidine, oxetane, epoxide, dioxane, imidazolone, imidazolinedione ....

The compounds of formula (I) can comprise one or more asymmetric carbon atoms. They can therefore exist as enantiomers or diastereoisomers. These enantiomers, diastereoisomers, and mixtures thereof, including racemic mixtures, form part of the invention.

The compounds of formula (I) may exist in the form of bases or addition salts with acids. Such addition salts are part of the invention.

These salts can be prepared with pharmaceutically acceptable acids, but the salts of other acids that are useful, for example, for the purification or the isolation of the compounds of formula (I) are also part of the invention.

In the products of formula (I) as defined above or below, the R 6 group is a 5- or 6-membered heteroaryl preferably chosen from pyridine, pyrazole, imidazole, thiophene, quinoline, thiazole or triazole groups, if appropriate. substituted by R2a. R6 may also represent C (O) NRIaRIb or an optionally substituted heterocycloalkyl or optionally substituted C (O) heterocycloalkyl as indicated above or hereinafter.

Among the compounds of formula (I) that are the subject of the invention, a first group of compounds consists of the compounds for which: R3 represents

1. hydrogen;

2 F ;

3. Cl;

4. Br;

5. (Cl-ClO) alkyl;

6. OR2a;

7. NRIaRIb;

8. CO2Rla;

9. CONRIaRIb;

Aryl optionally mono or di substituted with R2a R2b;

11. Heteroaryl optionally mono or di substituted with R2a R2b; and / or R6 represents a heteroaryl group, especially a pyridine, pyrazole, imidazole thiophene, quinoline, thiazole or triazole group.

Among the compounds of formula (I) which are subjects of the invention, a second group of compounds is constituted by the compounds for which

- R4 represents

1. hydrogen

2. Cl

3. ORIa

4. (Cl-ClO) alkyl

5. (C2-C6) alkenyl

6. (C2-C6) alkynyl

7. (C3-C7) cycloalkyl

8. CORIa;

9. CO ₂ RIa

10. NRIaRIb

11. CO (NRIaRIb)

12. heterocycloalkyl

13. aryl

14. heteroaryl each being optionally substituted with R2a, R2b and R2c and / or R6 represents a heteroaryl group, especially a pyridine, pyrazole, imidazole or triazole group.

Among the compounds of formula (I) that are the subject of the invention, a third group of compounds consists of the compounds for which R2a, R2b and R2c are chosen from

1. F;

2. Cl:

3. (Cl-ClO) alkyl;

4. OH;

5. O-alkyl;

6. NH2;

7. NHSO2alkyl;

8. NHSO2cycloalkyl;

9. NHSO2aryl;

10. NHC (O) alkyl;

11. NHC (O) cycloalkyl;

12. CF3;

13. C02alkyl; 14. C (O) NHalkyl

Wherein each heterocycloalkyl is optionally substituted with R3a, R3b and R3c, selected from

1. F;

2. Cl;

3. (Cl-ClO) alkyl;

4. OH;

5. O-alkyl;

6. NH2;

7. NH- (alkyl (C _r Cio) cycloalkyl or (C ₃ -C _7));

8. N (alkyl (C _r Cio) cycloalkyl or (C ₃ -C ₇₎₎ _2;

9. heterocycloalkyl.

Among the compounds of formula (I) that are the subject of the invention, a first group of compounds is constituted by the compounds for which: R 3 represents

1. hydrogen

2 F ;

3. Cl;

4. Br;

5. (Cl-ClO) alkyl;

6. OR2a

7. NRIaRIb

8. CO2Rla

9. CONRIaRIb ... and / or R6 represents a heteroaryl group, especially a pyridine, pyrazole imidazole or triazole group.

Among the compounds of formula (I) which are subjects of the invention, a second group of compounds is constituted by the compounds for which - R 4 represents

1. hydrogen

2. Cl

3. ORIa

4. (Cl-ClO) alkyl

5. (C2-C6) alkenyl

6. (C2-C6) alkynyl

7. (C3-C7) cycloalkyl

8. CORIa;

9. CO ₂ RIa

10. NRIaRIb

11. CO (NRIaRIb)

12. heterocycloalkyl

13. aryl

Wherein each heteroaryl is optionally substituted with R 2a, R 2b and R 2c and / or R 6 represents a heteroaryl group, especially a pyridine, pyrazole imidazole or triazole group.

Among the compounds of formula (I) that are the subject of the invention, a third group of compounds is constituted by the compounds for which

R2a, R2b and R2c are selected from 1. F; 2. Cl:

3. (Cl-ClO) alkyl;

4. OH;

5. O-alkyl

6. NH2;

7. NHSO2alkyl;

8. NHSO2cycloalkyl;

9. NHSO2aryl;

10. NHC (O) alkyl;

11. NHC (O) cycloalkyl;

12. CF3;

13. CO2alkyl;

14. C (O) Nhalkyl

15. heterocycloalkyl

Among the compounds of formula (I), the following compounds may be independently of one another:

N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} methanesulfonamide;

N- {4- [3-methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} methanesulfonamide;

4- (3,5-dimethoxyphenyl) -3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

4-cyclopropyl-3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; N-cyclopropyl-4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] benzenesulfonamide;

- 3-hydroxy-2,2-dimethylpropyl 6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine-3-carboxylate;

4-methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenol;

4 - [(E) -2-Cyclopropylethenyl] -3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

4- (3,5-difluorophenyl) -3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

6-methylpropan-2-yl 6-pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] -dipyridine-3-carboxylate;

3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] butane-1,2-diol;

[3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] (phenyl) methanone;

3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] benzenesulfonamide;

3- (morpholin-4-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-4- (morpholin-4-yl) -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

2-methylpropyl 6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridine-3-carboxylate; N-methyl-N-propyl-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-amine;

Ethyl 6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine-3-carboxylate; 6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-4-methyl-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

4-chloro-3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-4 - [(E) -2-phenylethenyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-chloro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

- (2E) -3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] prop-2-enoate ethyl;

3-fluoro-4- [3- (morpholin-4-yl) phenyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine-3-carboxylic acid;

[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] methanol;

Methyl 6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine-3-carboxylate; N-methyl-N-propyl-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine-3-carboxamide;

3-fluoro-N-methyl-N-phenyl-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine-4-carboxamide;

4- {methyl [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] amino} -1- (pyrrolidin-1-yl) ) butanone;

6- (furan-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

[3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] (morphol-4-yl) methanone;

6- (5-fluoropyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

2- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] propan-2-ol;

6- (6-fluoropyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; N, N-diethyl-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-amine; 3- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-b '] dipyridine;

3-methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-c: 5,4-c] dipyridine;

1-chloro-N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} methanesulfonamide;

3- (4-methylpiperazin-1-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} cyclopropanesulfonamide;

N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] -2-methoxyphenyl} methanesulfonamide ;

N- {4- [3-fluoro-6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl methanesulfonamide;

3-fluoro-6- (5-methoxypyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- (4-methoxypyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

6- (1-Benzyl-1H-pyrazol-4-yl) -3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- [1- (2-methylpropyl) -1H-pyrazol-4-yl] -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 3-fluoro-6- [5- (methylsulfanyl) pyridin-3-yl] -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] -2-methylbut-3-yn- 2-ol;

4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] -2-methylbut-3-yn- 2-amme; N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] -2-methylbut-3 -yn-2-ylmmethanesulfonamide;

3-fluoro-4- [3-methyl-3- (piperazin-1-yl) but-1-yn-1-yl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-di] b: 5.4- [c] dipyridine;

4- [3-Methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] -2-methylbut-3-yn- 2-ol;

4- [3-Methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] -2-methylbut-3-yn- 2-amme; N- {4- [3-methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] -2-methylbut-3 -yn-2-ylmmethanesulfonamide;

3-Methoxy-4- [3-methyl-3- (piperazin-1-yl) but-1-yn-1-yl] -6- (pyridin-3-yl) -9H-pyrrolo b: 5.4- [c] dipyridine;

3-fluoro-4- [4- (4-methylpiperazin-1-yl) piperidin-1-yl] -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5.4. dipyridine;

2- (4- {1- [3-Fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] piperidm-4 (1-piperazol-1-yl) ethanol;

3-Fluoro-4- [4- (morpholin-4-yl) piperidin-1-yl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] ] dipyridme;

3-fluoro-4- [4- (propan-2-yl) piperazin-1-yl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] ] dipyridme;

4- (4-cyclopropylpiperazin-1-yl) -3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

4- (4-ethylpiperazin-1-yl) -3-fluoro-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-4- [4- (1-methylpiperidin-4-yl) piperazin-1-yl] -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5.4 dipyridine;

3-methoxy-4- [4- (4-methylpiperazin-1-yl) piperidin-1-yl] -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5.4- dipyridine;

2- (4- {1- [3-Methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] piperidm-4 piperazin-1-yl) ethanol;

3-methoxy-4- [4- (morpholin-4-yl) piperidin-1-yl] -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] ] dipyridine;

3-methoxy-4- [4- (1-methylpiperidin-4-yl) piperazin-1-yl] -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4- dipyridine;

3-methoxy-4- [4- (propan-2-yl) piperazin-1-yl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] ] dipyridme;

4- (4-cyclopropylpiperazin-1-yl) -3-methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

4- (4-ethylpiperazin-1-yl) -3-methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-methoxy-4- [4- (methylsulfonyl) piperazin-1-yl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-4- [4- (methylsulfonyl) piperazin-1-yl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} propanoic acid; 3-fluoro-4- (6-methoxypyridin-3-yl) -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; N- {3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} methanesulfonamide;

3-fluoro-4- (4-methylthiophen-2-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 3-fluoro-4- (1H-indol-6-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

- {2- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} methanol;

3-fluoro-4- (4-methylthiophen-3-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] -N, N-dimethylaniline;

3-fluoro-4- (5-methylfuran-2-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-4- (1-methyl-1H-indol-5-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-4- (1-methyl-1H-pyrazol-4-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] benzyl} acetamide; N- {3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] benzyl} methanesulfonamide;

3-fluoro-4- (2-methoxyphenyl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

4- (2-Ethoxypyridin-3-yl) -3-fluoro-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

4 - ({3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] phenyl} amino acid) -4-oxobutanoic acid;

N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] benzyl} methanesulfonamide;

- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] phenyl} (morphol-4-yl) ) methanone;

3-fluoro-4- (1-methyl-1H-pyrazol-5-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

1- {2- [3-Fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} -N, N- dimethylmethanamine;

2- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] benzonitrile.

3- (4-methylpiperazin-1-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} cyclopropanesulfonamide;

3-fluoro-6- (5-methoxypyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- (4-methoxypyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 6- (1-Benzyl-1H-pyrazol-4-yl) -3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- [1- (2-methylpropyl) -1H-pyrazol-4-yl] -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- [5- (methylsulfanyl) pyridin-3-yl] -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 3-Fluoro-6- {1- [2- (morpholin-4-yl) ethyl] -1H-pyrazol-4-yl} -9H-pyrrolo [2,3-b: 5,4-c] dipyridine ;

3-fluoro-4- (piperidin-1-yl) -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] -2-methylbut-3-yn- 2-amme; 4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] -2-methylbut-3-yn- 2-ol;

4- [3- (4-ethylpiperazin-1-yl) -3-methylbut-1-yn-1-yl] -3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3] -b: 5,4-c '] dipyridine;

3- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} propanoic acid;

3-fluoro-4- (6-methoxypyridin-3-yl) -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N- {3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} methanesulfonamide;

3-fluoro-4- (4-methylthiophen-2-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-4- (1H-indol-6-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-4- (1-methyl-1H-pyrazol-4-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] benzyl} acetamide;

N- {3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] benzyl} methanesulfonamide;

4 - ({3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] phenyl} amino acid) -4-oxobutanoic acid; N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] benzyl} methanesulfonamide;

N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} -2-methylpropanamide ;

3-fluoro-4,6-di (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N- {2- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} methanesulfonamide; 3-fluoro-4- (1H-pyrazol-4-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-4- [3- (methylsulfonyl) phenyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-4- (2-methoxypyrimidin-5-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

5- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] pyrid-2-ammine;

3-fluoro-4- [4- (1-methylpiperidin-4-yl) piperazin-1-yl] -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5.4 c '] dipyridine;

3-fluoro-4- [4- (morpholin-4-yl) piperidin-1-yl] -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] ] dipyridme;

N, N-diethyl-2- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] piperazin-1-ylkethanamine;

3-fluoro-4- (4-methyl-1,4-diazepan-1-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] bipyridine;

2- {4- [3-Fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] piperazin-1-yl} ethanol;

3-fluoro-4- [4- (4-methylpiperazin-1-yl) piperidin-1-yl] -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5.4. c '] dipyridine;

N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} -N-methylmethanesulfonamide ;

3- (piperazin-1-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-amine;

4- (1,4'-Bipiperidin-r-yl) -3-fluoro-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

1- [3-fluoro-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] -N, N-dimethylpiperidm-4- amine;

3-fluoro-6- (pyridin-3-yl) -4- [4- (pyrrolidin-1-yl) piperidin-1-yl] -9H-pyrrolo [2,3-b: 5,4-c] ] dipyridme;

3-Fluoro-4- {4- [3- (piperidin-1-yl) propyl] piperazin-1-yl} -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b] 4- [4-] dipyridine;

3-Fluoro-4- {4- [3- (morpholin-4-yl) propyl] piperazin-1-yl} -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b] 4- [4-] dipyridine; 3- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] piperazin-1-yl} N, N-dipropylpropan-1-amine;

3-ethoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-iodo-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- {1- [2- (Morpholin-4-yl) ethyl] -1H-pyrazol-4-yl} -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5, 4- [dipyridine;

3- (1-methyl-1H-pyrazol-3-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N, N-diethyl-3- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] piperazin-1-yl} propan-1-amine;

N, N-diethyl-2- {4- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] -1H-pyrazol 1-yethanamine;

3-fluoro-4-methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- [1- (2-methylpropyl) -1H-pyrazol-4-yl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- [4- (morpholin-4-yl) phenyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; N-propyl-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-amine;

3- {4- [4- (propan-2-yl) piperazin-1-yl] phenyl} -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] '] dipyridme;

6- (pyridin-3-yl) -3- (2,2,2-trifluoroethoxy) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridine-6-carbonitrile;

3- (2-methoxyethoxy) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- {1- [3- (4-methylpiperazin-1-yl) propyl] -1H-pyrazol-4-yl} -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5.4- [c] dipyridine;

{3- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] phenyl} methanol;

N, N-diethyl-3- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-yl] benzamide; 3- (3,5-dimethyl-1H-pyrazol-4-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

2- {3,5-dimethyl-4- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] -1H-pyrazol 1-yl) -N, N-diethylethanamine;

3-methoxy-6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

4- {6- [1- (prop-2-en-1-yl) -1H-pyrazol-4-yl] -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4 methyl benzoate;

N, N-diethyl-2- [4- (3-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) -3,5-dimethyl-1H-pyrazol 1-yl] ethanamine; N- [2- (dimethylamino) ethyl] -2- [4- (3-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) -1H-pyrazol 1-acetamide;

3- (1H-pyrazol-4-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N, N-diethyl-3- {4- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] -1H-pyrazol propan-1-amine;

N, N-diethyl-3- [4- (3-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) -1H-pyrazol-1-yl] propan -the mine;

9H-pyrrolo [2,3-b: 5,4-c] dipyridine-6-carboxylic acid;

N- [3- (dimethylamino) propyl] -N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridm] [Phenyl] methanesulfonamide;

(4-methylpiperazin-1-yl) (9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) methanone;

5- [4- (3-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) -1H-pyrazol-1-yl] pentan-1-amine;

- {5- [4- (3-Methoxy-9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-6-yl) -1H-pyrazol-1-yl] pentyl} carbamate of 2- methylpropan-2-yl;

3-Methoxy-6- {1- [2- (1-methylpiperidin-2-yl) ethyl] -1H-pyrazol-4-yl} -9H-pyrrolo [2,3-b: 5,4-c] ] dipyridine;

3- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenoxy} -N, N dimethylpropan-1-amine;

4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenol;

2- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenoxy} -N, N dimethylethanamine;

3- {1 - [(1-ethylpyrrolidin-2-yl) methyl] -1H-pyrazol-4-yl} -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5, 4- [dipyridine;

3-fluoro-6- (pyridin-3-yl) -4- {4- [2- (pyrrolidin-1-yl) ethoxy] phenyl} -9H-pyrrolo [2,3-b: 5,4-c]; '] dipyridine;

3-fluoro-6- (thiophen-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

4- {4- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] phenyl} piperazine-1-carboxylate of 2- methylpropan-2-yl;

3- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenoxy} -N, N 2-trimethylpropan-1-amine;

3-Fluoro-4- {4- [2- (morpholin-4-yl) ethoxy] phenyl} -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] '] dipyridine;

N, N-diethyl-2- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenoxy} ethanamine; N- [2- (dimethylamino) ethyl] -5- [3-fluoro-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4- yl] pyridine-2-carboxamide;

1- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenoxy} -3- ( morphol-4-yl) propan-2-ol;

N-ethyl-3- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenoxy} propan-1-amino;

4- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] phenol;

3- [4- (piperazin-1-yl) phenyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- (isoquinolin-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N, N-dimethyl-3- {4- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] phenoxy} propanediol the mine;

3- {4- [3- (piperidin-1-yl) propoxy] phenyl} -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- {4- [2- (Morpholin-4-yl) ethoxy] phenyl} -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- {4- [3- (Morpholin-4-yl) propoxy] phenyl} -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 3- {4- [2- (1H-imidazol-1-yl) ethoxy] phenyl} -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] bipyridine;

3- (4- {3- [4- (methylsulfonyl) piperazin-1-yl] propoxy} phenyl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4- c '] dipyridine;

N, N-diethyl-2- {3- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] phenoxy} ethanol;

4- {3- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] phenyl} piperzme-1-carboxylate of 2- methylpropan-2-yl;

N, N, 4-triethyl-5- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-yl] pyrid-2-amine ;

3- [3- (piperazin-1-yl) phenyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine hydrochloride;

N, N-diethyl-2 - ({4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl} 2-methylbut-3-yn-2-yl} oxy) ethanamine;

4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] -N- (prop-2-en) -l-yl) anilme; N- (2-methylpropan-2-yl) -5- (9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) pyridine-3-carboxamide;

5- (3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) -N- (2-methylpropan-2-yl) pyridine-3-carboxamide;

3-fluoro-6- (1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

(2E) -N- [4- (dimethylamino) butyl] -3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c]] dipyridm-4-yl] prop-2-enamide;

6-chloro-3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 3- {4- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-yl] phenoxy} propan-1-amine;

Among the compounds of formula (I), the following compounds may also be independently of one another:

3- {1- [3- (4-methylpiperazin-1-yl) propyl] -1H-pyrazol-4-yl} -6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [ 2,3-b: 5,4-c '] dipyridine;

3- [3- (4-methylpiperazin-1-yl) phenyl] -6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] ] dipyridine;

N, N-diethyl-2- {4- [6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3- yl] -1H-pyrazol-1-yl} ethanamine;

6- (1-methyl-1H-pyrazol-4-yl) -3- {4- [3- (morpholin-4-yl) propoxy] phenyl} -9H-pyrrolo [2,3-b: 5.4 dipyridine;

N, N -diethyl, -IS-Cό-Cl-methyl-1H-pyrazol-yl-pH-pyridol-5S-diol-4'-dipyridin-5-yl] phenoxy} ethanamine;

3-Fluoro-6- (1-methyl-1H-pyrazol-4-yl) -4- {4- [3- (piperidin-1-yl) propyl] piperazin-1-yl} -9H-pyrrolo [2] , 3-b: 5,4-c '] dipyridine;

4- [3- (4-ethylpiperazin-1-yl) -3-methylbut-1-yn-1-yl] -3-fluoro-6- (1-methyl-1H-pyrazol-4-yl) -9H pyrrolo [2,3-b: 5,4-c '] dipyridine;

N- [3- (dimethylamino) propyl] -N- {4- [3-fluoro-6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5, 4- [dipyridin-4-yl] phenyl} methanesulfonamide;

N-ethyl-3- {4- [3-fluoro-6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine) 4-yl] phenoxy} propan-1-amine;

N, N-diethyl-2- {4- [3-fluoro-6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c]] dipyridin-4-yl] phenoxy} ethanamine;

3- {4- [3-Fluoro-6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenoxy-N, N, 2-trimethylpropan-1-amine;

1- {4- [3-Fluoro-6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenoxy-3- (piperidin-1-yl) propan-2-ol;

1- {4- [3- (2-methoxyethoxy) -6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine); 4-yl] phenoxy-3- (piperidin-1-yl) propan-2-ol;

3- (2-Methoxyethoxy) -6- (1-methyl-1H-pyrazol-4-yl) -4- {4- [3- (piperidin-1-yl) propyl] piperazin-1-yl} -9H -pyrrolo [2,3-b: 5,4-c '] dipyridine;

4- [3- (4-ethylpiperazin-1-yl) -3-methylbut-1-yl-1-yl] -3- (2-methoxyethoxy) -6- (1-methyl-1H-pyrazol) -4- yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridine;

N- [3- (dimethylamino) propyl] -N- {4- [3- (2-methoxyethoxy) -6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3- b: 5,4-c '] dipyridin-4-yl] phenyl} methanesulfonamide; N-ethyl-3- {4- [3- (2-methoxyethoxy) -6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c]; dipyridin-4-yl] phenoxypropan-1-amine;

3- {4- [3- (2-methoxyethoxy) -6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 4-yl] phenoxy} -N, N, 2-trimethylpropan-1-amine;

N, N-diethyl-2- {4- [3- (2-methoxyethoxy) -6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5.4 [α] dipyridin-4-yl] phenoxy} ethanamine;

3-amino-1- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] phenyl} pyrrolidine-2,5-dione;

4 - ({[3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-4-yl] oxy} methyl) -N, N-dimethylaniline;

3-Fluoro-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl [4- (dimethylamino) phenyl] carbamate;

3-Fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl [3- (dimethylamino) propyl] carbamate;

3 - [(3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) carbonyl] -1,5,5-trimethylimidazolidine-2,4-dione;

3 - [(3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) carbonyl] -1-methylimidazolidine-2,4-dione;

3 - [(3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) carbonyl] -5,5-dimethyl-1- (propan-2-yl) imidazolidine-2,4-dione;

1 - [(3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) carbonyl] -4,4-dimethyl-3- (propan-2-yl) imidazolidin-2-one;

1 - [(3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) carbonyl] -3,4,4-trimethylimidazolidin-2-one;

1 - [(3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) carbonyl] -3-methylimidazolidin-2-one;

3-fluoro-6- (1-methyl-1H-imidazol-5-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-Fluoro-6- {1-methyl-5- [3-methyl-3- (4-methylpiperazin-1-yl) but-1-yn-1-yl] -1H-pyrazol-4-yl} -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

6- (5-chloro-1-methyl-1H-pyrazol-4-yl) -3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

6- (5-bromo-1-methyl-1H-pyrazol-4-yl) -3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N- {4- [3- (dimethylamino) propoxy] benzyl} -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-amine;

N- {4- [2- (dimethylamino) ethoxy] benzyl} -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-amine; 6- (pyridin-3-yl) -N - {[2- (pyridin-4-yl) cyclopropyl] methyl} -9H-pyrrolo [2,3-b: 5,4-c '] dipyridm-3- amine;

N- [3-fluoro-4- (piperazin-1-yl) benzyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridm-3 -amine;

6- (pyridin-3-yl) -N - {[1- (pyridin-3-ylmethyl) -1H-pyrrol-2-yl] methyl} -9H-pyrrolo [2,3-b: 5,4- dipyridin-3-amine;

N- {4 - [(dimethylamino) methyl] benzyl} -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-amine;

4-methyl-N1- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] pentane-1,4-diam;

N- (4-methyl-4-nitropentyl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-ammine;

N, N-dimethyl-N '- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c'] dipyridin-3-yl] butane-1,4-4 diamme;

piperazin-1-yl [4 - ({[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-yl] amino} methyl) phenyl ] methanone;

N- [4- (aminomethyl) benzyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-amine;

[4- (6- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-yl] amino] methyl) benzyl] carbamate methylpropan-2-yl;

4 - {[4 - ({[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] amino} methyl) phenyl] carbonyl 2-methylpropan-2-yl piperazine-1-carboxylate;

N- [4- (dimethylamino) benzyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-amine;

N- {4 - [(4-methyl-1,4-diazepan-1-yl) methyl] benzyl} -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5.4 dipyridin-3-amine;

4- (4-methyl-1,4-diazepan-1-yl) -N- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine Benzylamide;

N- [4- (4-methyl-1,4-diazepan-1-yl) benzyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] ] dipyridin-3-amine;

3- (4-methyl-1,4-diazepan-1-yl) -N- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine Propanamide;

3 - [(4-methyl-1,4-diazepan-1-yl) methyl] -N- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] benzamide;

N- {3 - [(4-methyl-1,4-diazepan-1-yl) methyl] benzyl} -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5.4 dipyridin-3-amine;

N- [2- (4-methyl-1,4-diazepan-1-yl) ethyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] ] dipyridm-3-amine;

6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine-3-carbonitrile;

6- (3,5-dimethyl-1H-pyrazol-4-yl) -3- (pyridin-3-yl) -9H-beta-carboline;

2- {3- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] phenoxy} ethanamine; 3- (4 - {[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] oxy} phenyl) propan-1-ol ;

N, N-dimethyl-2- (4 - {[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] oxy} phenyl ) ethanamine;

2- (4 - {[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] oxy} phenyl) acetamide; N-methyl-2- (4 - {[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] oxy} phenyl) acetamide ;

N-cyclopropyl-2- (4 - {[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] oxy} phenyl) acetamide ;

N- (propan-2-yl) -1- (4 - {[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl} oxy] phenyl) propan-2-amine;

6- (pyridin-3-yl) -3- {4- [2- (pyrrolidin-1-yl) propyl] phenoxy} -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N, N-diethyl-3- (4 - {[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] oxy} phenyl ) propan-1-amino;

N, N-diethyl-2 - {[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-yl] oxy} ethanol;

The subject of the present invention is also the processes for preparing the products of formula (I) as defined above and described in particular in Schemes 1 to 11 below. The subject of the present invention is in particular the process for the preparation of the products of formula (I) as defined above and described in scheme 1 below in which the substituents R 3 and R 4 have the meanings indicated above or above. after, and R represents either the values of R6 as defined above or the following values: OH, OCH ₃ , OS (O) ₂ CF ₃ , Cl, SCH ₃ , CN.

The tricyclic nucleus synthesis strategy is based on two coupling reactions; a carbon-carbon bond is first created between two suitably chosen pyridines, then the formation of an intramolecular carbon-nitrogen bond leads to the 9H-pyrrolo [2,3-b: 5,4-c '] dipyridine ( see Figure 1 below).

Diagram 1

The starting products D1 and D2 of Scheme 1 can be commercial or can be prepared according to the usual methods known to those skilled in the art.

The subject of the present invention is also the processes for preparing Dl and / or D2 as defined in particular in Schemes 2 and 7 below. The subject of the present invention is therefore also, as new industrial products, certain compounds D1 and / or D2 as defined above or hereinafter.

The subject of the present invention is also, as new industrial products, the synthetic intermediates D3 in which the substituents R3, R4 and R have the meanings indicated above or below. The subject of the present invention is also, as new industrial products, synthetic intermediates D3 in which the substituent R3 represents a fluorine atom or a methoxy radical, and the substituent R4 represents a hydrogen atom, R being chosen from values defined above.

The compounds D4 represent products of formula (I) as defined above when R represents the values of R6 as defined above, R3 and R4 having any of the meanings indicated above.

The subject of the present invention is also, as new industrial products, the synthetic intermediates D4 in which R represents the following values: OH, OCH ₃ ,

OS (O) ₂ CF ₃ , Cl, SCH ₃ , CN, R 3 and R 4 having any of the meanings indicated above.

The process for preparing the compounds according to the invention consists in a first step of reacting the following products: Me ₃ SnCl

Figure 2 In a second step to achieve the next step

Figure 3 where the Josiphos is a compound of the following formula:

When the R3 and R4 groups are not present before the coupling-cyclization sequence, the following strategies have been developed. In the case of position 4, after protection of position 9, a metalation is effected by the action of a strong base in the presence of a suitable ortho-director group R3. When the anion is trapped, for example, by action of the diiodode, an iodinated intermediate in position 4 is then obtained, this compound allows the preparation of numerous compounds functionalized at 4 via coupling reactions catalyzed by organometallic complexes (Suzuki reaction introduction of amine by Hartwig-Buchwald reaction, introduction of alkyne by reaction of Sonogashira).

Figure 5

The 3-position structure variations are made from the 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridine derivative obtained by the action of the dibrome in acetic acid on 6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine. Again, coupling reactions catalyzed by palladium complexes (introduction of aryl or heteroaryl by reaction of Suzuki, introduction of amine by Hartwig-Buchwald type reaction) or copper (introduction of alkoxy group) make it possible to obtain different functionalized compounds in position 3.

Figure 6

The first step of the process for preparing the compounds having a unit other than the (3- pyridinyl) group at the 6-position according to the invention consists in one of the following two reactions:

Figure 7

In a second step, coupling Stille with a 2-amino-3- (bromo or iodo) -pyridine derivative optionally substituted at the 4- or 5-position, followed by an intramolecular aryl amination reaction catalyzed by either a palladium complex, either with copper (I) iodide:

Figure 8

The r-methyl-1 H-pyrazol-4'-yl unit (or any other aryl or heterorayl unit that can be introduced by a palladium complex catalyzed coupling reaction) is installed by means of a three-stage sequence comprising : a demethylation reaction, the formation of a triflate derivative and a Suzuki coupling reaction. The 6-carboxamide group synthesis is also possible from triflate: a nitrile function is first introduced by reacting zinc cyanide in the presence of a palladium complex, in the next step the nitrile is hydrolyzed in an acid medium to give the corresponding carboxylic acid. The last step is amide formation via the acyl chloride obtained by the action of thionyl chloride.

Figure 9

The 3-fluoro-6-methoxy-9H-pyrrolo [2,3-b: 5,4-c '] dipyridine derivative can also be used in a metalation-iodination reaction already described above. After a Suzuki reaction, the compound obtained can undergo the same sequence as before (demethylation, formation of triflate and introduction of heteroaryl by Suzuki coupling).

Figure 10

In certain cases, the variations in the 4-positions can be carried out via a triflate group obtained from the corresponding methoxy. In this case, the coupling-cyclization sequence is carried out with the stannylated derivative described above and 2-amino-3-iodo-4-methoxypyridine. The tricyclic dimethoxy compound is then converted to the corresponding ditriflate in two steps. This ditriflate reacts preferentially in position 4 during a Suzuki coupling, which makes it possible to selectively and sequentially introduce an aryl group at the 4-position and a heteroaryl group at the 6-position.

Figure 11

According to another of its aspects, the present invention relates to pharmaceutical compositions comprising, as active principle, a compound according to the invention. These pharmaceutical compositions contain an effective dose of at least one compound according to the invention, or a pharmaceutically acceptable salt, of said compound, as well as at least one pharmaceutically acceptable excipient.

The said excipients are chosen according to the pharmaceutical form and the desired mode of administration, from the usual excipients which are known to those skilled in the art.

In the pharmaceutical compositions of the present invention for oral, sublingual, subcutaneous, intramuscular, intravenous, topical, local, intratracheal, intranasal, transdermal or rectal administration, the active ingredient of formula (I) above, or its salt, may be administered in unit dosage form, in admixture with conventional pharmaceutical excipients, to animals and humans for the treatment of the above disorders or diseases.

Suitable unit dosage forms include oral forms such as tablets, soft or hard capsules, powders, granules and oral solutions or suspensions, sublingual, oral, intratracheal, intraocular, intranasal forms of administration. by inhalation, topical, transdermal, subcutaneous, intramuscular or intravenous administration forms, rectal administration forms and implants. For topical application, the compounds according to the invention can be used in creams, gels, ointments or lotions. These drugs find their therapeutic use, especially in the treatment of cancers sensitive to the deregulation of PIM kinases. The inhibitors of Pim kinases that are the subject of the present invention are useful for the treatment of cancer, in particular leukemias, lymphomas and myelomas. They can also be used for the treatment of various solid tumors, including head and neck cancers, colon cancer, prostate cancer, pancreatic cancer, liver cancer and oral cancer, for example. Since cancer remains a disease for which existing therapies are inadequate, it is clearly necessary to identify new inhibitors of Pim kinases that are effective in the treatment of cancer.

The subject of the present invention is therefore a medicinal product, characterized in that it comprises a compound of formula (I) as defined above, or a salt of addition of this compound to a pharmaceutically acceptable acid.

The subject of the present invention is therefore pharmaceutical compositions containing, as active principle, a compound of formula (I) as defined above, as well as at least one pharmaceutically compatible excipient.

The present invention therefore relates to these pharmaceutical compositions used for the treatment of cancer.

The present invention therefore relates to the use of a compound of formula (I) as defined above for the preparation of a medicament for the treatment of diseases sensitive to the deregulation of PIM kinases.

The present invention therefore relates to the use of a compound of formula (I) as defined above for the preparation of a medicament for the treatment of cancer

The subject of the present invention is therefore the use of the products of formula (I) as defined above, for the preparation of medicaments intended for the chemotherapy of cancers.

The subject of the present invention is therefore the compounds of formula (I) as defined above as kinase inhibitors.

The subject of the present invention is therefore the compounds of formula (I) as defined above as inhibitors of PIM kinases.

The present invention, according to another of its aspects, also relates to a method of treatment of the pathologies indicated above which comprises the administration to a patient of an effective dose of a compound according to the invention, or one of pharmaceutically acceptable salts thereof. The following examples describe the preparation of certain compounds according to the invention. These examples are not limiting and only illustrate the present invention. The numbers of the compounds exemplified refer to those given in the table below, which illustrates the chemical structures and the physical properties of some compounds according to the invention.

EXPERIMENTAL PART

GENERALITIES: All reactions are carried out with anhydrous solvents from the Acros Organics AcroSeal range. The solvents used for extractions and chromatographies come from SDS. The purifications on silica gel are carried out using silica cartridges (silica gel 60 15-40 .mu.m). Preparative HPLC purifications are performed on Macherey-Nagel columns (NUCLEODUR Cl 8 phase) or other phases (Chiralcel OD-I or OJ-H or AS-H, Chiralpak, Kromasil Ci ₈ ) with appropriate eluents.

LC-MS-DAD-ELSD analysis: 2 possible experimental conditions:

O LC-MS-DAD-ELSD analysis (or LC-MS (7 min)): MS = Waters ZQ, mode +/- electrospray, mass range m / z = 100-1200; LC = Agilent HP 1100, LC column = X Bridge 18 C Waters; 3.0 x 50 mm -2.5 μm; oven LC = 60 ⁰ C; flow rate = 1.1 ml / minute. Eluents: A = Water + 0.1% Formal Ac B = Acetonitrile with the following gradient:

Time A% B%

0.0 95 5.0

5.0 5.0 100

5.5 5.0 100

6.5 95.0 5.0

7.0 95.0 5.0 θ LC-MS-DAD-ELSD (or LC-MS (7 min)) analysis: MS = Platform II Waters Micromass, electrospray +/-, mass range m / z = 100-100; LC Alliance 2695 Waters; Column X Terra 18C Waters; 4.6 mm. 75 mm 2.5 μm; oven LC = 60 ° C; flow rate = 1.0 ml / minute. Eluents: A = Water + 0.1% Formal Ac B = Acetonitrile with the following gradient:

Time A% B%

0 95 5

6.0 5 95

8.0 5 95

9.0 95 5

13.0 95 5

^ UPLC-MS-D AD-ELSD analysis: 2 possible experimental conditions:

O UPLC-MS-D AD-ELSD Analysis: MS = Quattro First XE Waters, electrospray +/-, mass range m / z = 100-1100; UPLC Waters, Acquity column UPLC BeH C18 1.7 μm 3mm.50mm, UPLC oven = 70 ° C, flow rate = 0.7 ml / minute. Eluents: A = Water + 0.1% Ac Formic B = Acetonitrile + 0, 1% Ac Formic with the gradient:

Time A% B%

0 95 5

5 0 100

5.5 95 5

6.0 95 5 θ UPLC-MS-DAD-ELSD analysis: MS = SQD Waters, electrospray +/-, mass range m / z = 100-100; UPLC-Waters Acquity column UPLC Beh C18 1.7 μm 3 mm.50 mm, UPLC oven = 70 ° C, flow rate = 1 ml / minute.

Eluents: A = Water + 0.1% Ac Formal B = Acetonitrile + 0, 1% Ac Formic with the gradient: Time A% B%

0 95 5

0.8 50 50

1.2 0 100 1.85 0 100

1.95 95 5

2.00 95 5

For detection:

DAD considered wavelength λ = 210-400 nm

ELSD: Sedere SEDEX 85; nebulization temperature = 35 ° C; nebulization pressure = 3.7 bar

N.B: Depending on the structures analyzed, the dilution solvents are: dimethylsulfoxide; methanol; acetonitrile; dichloromethane.

METHODS OF SYNTHESIS

Synthesis of 5-chloro-4-trimethylstannyl-2- (3'-pyridyl) pyridine 2:

Step:

In a 20 ml microwave tube, 1.4 g of 2,5-dichloropyridine, 2.04 g of 3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan) are introduced under argon. -2-yl) pyridine, 0.76 g tetrakis (triphenylphosphine) palladium (O) and 7.7 g of cesium carbonate and then 15.5 ml of 1,4-dioxane and 0.7 ml of water. Microwave heating for 1 hour at 125 ° C. The reaction can also be carried out by conventional heating (time 6 hours at reflux of the solvent). After cooling, the reaction mixture is poured into 75 ml of a solution of 10% sodium bicarbonate and 25 ml of water, extracted twice with 100 ml of ethyl acetate, dried over sodium sulfate, filtered. and concentrated to dryness under reduced pressure. 2.8 g of a crude product which is purified by chromatography on silica gel, eluting with a mixture of heptane and ethyl acetate (70/30 by volume), thus gives 1, 2 g (67%) of 5-chloro-2- (3'-pyridinyl) -pyridine 1.

LC-MS-DAD-ELSD: 191 (+) = (M + H) (+) Tr (min) = 2.28

2nd step :

1.4 ml of diisopropylamine and 5 ml of tetrahydrofuran are introduced into a dry flask under an argon atmosphere equipped with magnetic stirring. The solution was cooled to -78 ° C and then 3.95 mL of n-butyllithium (2.5 M in hexane) was added. After stirring for 15 minutes, 1.45 g of 1 previously dissolved in 20 ml of tetrahydrofuran are added. After stirring for 2 hours, 10 ml of a solution of trimethyltin chloride at 1M in hexane is added. It is stirred for 1 hour at -78 ° C. The reaction medium is hydrolyzed with 120 ml of a solution of 10% ammonium chloride and 30 ml of water. It is extracted twice with 50 ml of ethyl acetate and then dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. 3.2 g of a crude product are obtained which is purified by chromatography on silica gel using a gradient of heptane and ethyl acetate eluent (from 100/0 to 70/30 by volume), 1.7 (63%) g of 5-chloro 4-trimethylstannyl-2- (3'-pyridinyl) pyridine 2.

LC-MS-DAD-ELSD: 354 (+) = (M + H) (+) (isotopic profile corresponding to a tin derivative) Tr (min) = 4.36

Example 1 to 8 (5a - 5h):

GENERAL PROCEDURE FOR THE SEQUENCE - STILL / CYCLING COUPLING

BY AMINATION IN THE CONDITIONS OF HARTWIG-BUCHWALD

10 mmol of 2-amino-3-halo (bromo or iodo) -pyridine 3a-h (see Table 1) are introduced into a 100 ml flask, 10.5 mmol of 5-chloro-4-trimethylstannyl-2- (3'-Pyridinyl) pyridine 2. 1 mmol tetrakis (triphenylphosphine) palladium (O) and 2 to 3 mmol copper iodide in 30 ml 1,4-dioxane. The reaction mixture is heated at 100 ^° C. for 1 night. After cooling, the reaction mixture is poured into 200 ml of a solution of 10% sodium bicarbonate and 25 ml of water, extracted twice with 200 ml of ethyl acetate, dried over sodium sulphate and filtered. and concentrated to dryness under reduced pressure. The crude product is purified by chromatography on silica gel using a gradient of eluent of ethyl acetate and methanol or of dichloromethane and methanol (100/0 to 90/10 by volume). The coupled products 4a-h are obtained in yields of between 40 and 75%. In a 150 ml dry flask, 5 mmol of the coupled product 4 are dissolved in 30 ml of 1,4-dioxane under an argon atmosphere. 0.35 mmol of palladium (II) acetate and 0.75 mmol of (R) - (-) - 1 - [(S) -2- (dicyclohexylphosphino) ferrocenyl] ethyl are introduced under argon in a dry tube. - di-tert-butylphosphine, 6 ml of 1,4-dioxane are added and the mixture is stirred for 10 minutes under argon. This catalyst solution is added to the solution of 3 as well as 7 to 12 mmol of potassium tert-butoxide. It is heated overnight at 100 ^° C. After cooling, 10 ml of methanol and 150 ml of ethyl acetate are added. The organic phase is washed with an aqueous solution of sodium bicarbonate, dried and evaporated. The crude product is purified by chromatography on silica gel using a gradient of eluents of ethyl acetate and methanol or of dichloromethane and methanol (from 100/0 to 90/10 by volume). The cyclized products 5a-h are detailed in Table 1 (yield between 35 and 80% depending on the substrates).

The cyclization can also be carried out using another catalytic system, in this case the product 4 (1 mmol) is loaded into a 5 ml microwave tube with 0.05 mmol of tris (dibenzylideneacetone) dipalladium (0), 0.11 mmol of 2-dicyclohexylphosphino-2- (N, N-dimethylamino) biphenyl and 1.5 mmol of potassium fert-butoxide. The tube is sealed and then placed under an argon atmosphere, then 4 mL of 1,4-dioxane is added. The mixture is heated in the microwave for 1 hour at 150 ^° C. The treatment and the purification of the compound 5 are carried out as described above. The yields are generally lower than those obtained with the Pd (OAc) ₂ / Josiphos system. All the steps of this sequence can be carried out either by heating in the microwave (between 110 and 150 ⁰ C) or conventional heating (reflux).

Table 1

Synthesis of 3e and 3f:

In a flask, 2.41 g of ethyl 2-amino-3-bromo-5-pyridine carboxylate 3d are introduced into 120 ml of methanol and 2.8 g of potassium hydroxide in 40 ml of water. Stirred by heating at 60 ^° C. for 3 hours. The methanol is evaporated. After cooling, 10 ml of 5N hydrochloric acid are added. The precipitate is filtered and 2.07 g of 6-amino-5-bromo-nicotinic acid is obtained. LC-MS-DAD-ELSD: 217 (+) and 219 (+) = (M + H) (+) Tr (min) = 1.71

For 3rd:

543 mg of 6-amino-5-bromo-nicotinic acid, 385 ml of methylpropylamine in 20 ml of dichloromethane are charged to a flask. After stirring, 1.05 g of 1- (3-dimethylamino-propyl) -3-ethyl-carbodiimide hydrochloride is added. After stirring overnight, the reaction mixture is poured into 50 ml of 10% sodium bicarbonate solution and 10 ml of water, extracted twice with 25 ml of dichloromethane, dried over sodium sulphate and filtered. and concentrated to dryness under reduced pressure. 859 mg of a crude product are obtained which is purified by chromatography on silica gel using a heptane / ethyl acetate eluent gradient (from 95/5 to 50/50 by volume), obtains 485 mg of 6-amino-5-bromo-N-methyl-N-propyl-nicotinamide 3e.

LC-MS-DAD-ELSD: 272 (+) = (M + H) (+) Tr (min) = 2.59

For 3f:

1.5 g of 6-amino-5-bromo-nicotinic acid and 10 ml of thionyl chloride are loaded into a flask. The mixture is refluxed for 3 hours. The excess thionyl chloride is evaporated and then taken up in 25 ml of tetrahydrofuran and 3.103 g of potassium tert-butoxide previously dissolved in 25 ml of tetrahydrofuran are added. After stirring for one hour, the mixture is concentrated to dryness under reduced pressure and purified by chromatography on silica gel using a gradient of heptane and ethyl acetate eluents (from 100/0 to 80/20 by volume). ), 230 mg of tert-butyl ester of 6-amino-5-bromo-nicotinic acid is thus obtained.

LC-MS-DAD-ELSD: 217 (+) and 219 (+) = (M + HC ₄ H ₉ ) (+) 273 and 275 = (M + H) (+) Tr (min) = 1.71 Synthesis of 3g:

In a dry monocolon and under argon, a solution of 15 mmol of N- (5-methoxy-pyridin-2-yl) -2,2-dimethyl-propionamide in anhydrous tetrahydrofuran (70 ml) is introduced by syringe. It is cooled to -78 ° C. and 37.5 mmol of tert-butyllithium (1.5 M in pentane) are then added over 15 minutes. The temperature is allowed to rise to 0 ^° C. and the mixture is left stirring for 2 hours. The reaction mixture is again cooled to -78 ° C. and then a solution of 37.5 mmol of diiodin in 5 ml of anhydrous tetrahydrofuran is added. The reaction mixture is then poured onto an aqueous solution of ammonium chloride which is extracted with ethyl acetate. The organic phase is washed with an aqueous solution of sodium thiosulfate, then dried over magnesium sulfate and concentrated under reduced pressure. The crude product is purified by chromatography on silica gel (gradient: dichloromethane to dichloromethane / methanol 95/5). 1.7 g (34%) of compound 3g are obtained.

UPLC-MS-DAD-ELSD: 334 (+) = (M + H) (+) Tr (min) = 0.88

Example 9: Synthesis of 3-bromo-6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-c'ldipyridine 6

360 mg of 5a, 15 ml of acetic acid and 10 ml of dimethylformamide are introduced into a flask. After stirring, 0.3 ml of bromine are added dropwise. After stirring for 3 hours at room temperature, the precipitate is filtered and then filtered with an aqueous solution of sodium thiosulfate and with water. After drying, 463 mg (97%) of 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 6 are obtained.

1H NMR (400MHz, DMSO -? / 6) δ ppm: 7.54 (dd, J = 8.0, 4.9Hz, 1H) 8.47 (dt, J = 8.0, 2.0Hz, 1H) 8.60 (dd, J = 4.9) , 2.0 Hz, 1H) 8.69 (d, J = 2.4Hz, 1H) 8.93 (s, 1H) 9.00 (d, J = 2.4Hz, 1H) 9.05 (s, 1H) 9.34 (d, J) = 2.0 Hz, 1H) 12.55 (m spread, 1H) LC-MS-DAD-ELSD: 323 (-) /... (MH) (-) / ...; 325 (+) /...= (M + H) (+) / ... (1 Br present) Example 10-12 (9a-9c)

GENERAL PROCEDURE FOR THE AMINATION REACTION IN CONDITIONS

BUCHWALD

In a 50 ml flask, 325 mg of 6 in 30 ml of dimethylformamide are introduced. 80 mg of sodium hydride are added under argon. After stirring for two hours, 0.194 ml of acetyl chloride in 2 ml of dimethylformamide are added. After stirring for two hours, the reaction mixture is poured into 50 ml of a solution of 10% sodium bicarbonate and 20 ml of water, extracted twice with 50 ml of ethyl acetate, dried over sulfate. magnesium, filtered and concentrated to dryness under reduced pressure. 355 mg of 1- (3-bromo-6-pyridin-3-yl-dipyrido [2,3-b: 4 ', 3'-d] pyrrol-9-yl) -ethanone 7 are obtained. next without purification.

In a 5 ml microwave tube, 0.25 mmol of 7, 17.5 μmol of tris (dibenzylidene acetone) dipalladium (O), 37.5 μmol of ligand (see Table 2) and 0.625 mmol of tert are introduced. potassium butoxide in 2 mL of 1,4-dioxane. Then, between 0.8 and 2.5 mmol of amine 8a-c is added (see Table 2). The mixture is heated in the microwave for 1 hour at 140 ^° C. After cooling, the reaction mixture is poured into 50 ml of a solution of 10% sodium bicarbonate and 20 ml of water, extracted twice with 60 ml. of ethyl acetate, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. The products 9a-c are purified by preparative HPLC and obtained with yields of between 7% and 30%.

Table 2

Synthesis Amine 8c:

Step 1 :

3 g of 4- (methylamino) -butyric hydrochloride acid, 7 g of potassium carbonate in 40 ml of 1,4-dioxane and 20 ml of water are introduced into a flask. Then 4.86 g of di-tert-butyl dicarbonate are added. After stirring for 6 hours, the dioxane is evaporated and then 30 ml of water are added. A 1M aqueous solution of potassium bisulfate is added until pH = 2. Extracted twice with 10 mL of ethyl acetate, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. 4.37 g of 4- (tert-butoxycarbonyl-methyl-amino) -butyric acid are obtained. 2nd step :

In a 100 ml flask, 1 g of 4- (tert-butoxycarbonyl-methyl-amino) -butyric acid is introduced into 10 ml of dimethylformamide, 1.925 g of [Dimethylamino- (1,2,3-triazolo [4 5- [1-pyridin-3-yloxy) -methylene] -dimethylammonium hexafluorophosphate, 713 mg of N, N-diisopropylethylamine and 360 mg of pyrrolidine. The solution is stirred overnight at room temperature. The reaction mixture is poured into 50 ml of water, extracted three times with 200 ml of ethyl acetate. It is taken up in dichloromethane and filtered through 2 cm of silica. Evaporate to dryness under vacuum. 806 mg of Methyl- (4-oxo-4-pyrrolidin-1-yl-butyl) -carbamic acid tert-butyl ester are thus obtained. Stage 3:

400 mg of Methyl- (4-oxo-4-pyrrolidin-1-yl-butyl) -carbamic acid tert-butyl ester, 5 ml of trifluoroacetic acid in 25 ml of dichloromethane are introduced into a flask. Stirred for 3 hours 30 minutes at room temperature. The reaction mixture is concentrated under reduced pressure. Purified by chromatography (SCX) eluting with a mixture of methanol and 2N ammonia. 125 mg of 4-methylamino-1-pyrrolidin-1-yl-butan-1-one 8c is obtained.

Example 13: Synthesis of 3-chloro-6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-c'ldipyridine 10:

To a solution of 493 mg of 5a in 20 ml of acetic acid and 5 ml of dimethylformamide are added dropwise 802 mg of N-chlorosuccinimide dissolved in 5 ml of dimethylformamide. The reaction mixture is then stirred at 25 ^° C. for 1 night. The suspension obtained is concentrated under reduced pressure, the dry extract is taken up in a methanol / dichloromethane mixture with silica Ig and then concentrated under reduced pressure in order to make a solid deposit on a column. The gross product is purified by chromatography on silica gel (gradient ethyl acetate 100% to ethyl acetate - methanol 90/10). The fractions containing the expected product are combined and concentrated under reduced pressure to give 380 mg of 3-chloro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine at 80% of purity NMR. The product obtained is taken up in 10 ml of DMSO, the insoluble matter is removed by filtration, the filtrate is purified by preparative HPLC to give 60 mg of 3-chloro-6- (pyridin-3-yl) -9H-pyrrolo [2 , 3-b: 5,4-c '] dipyridine 10 having the following characteristics:

IH NMR (400 MHz, DMSO -? / 6) δ ppm: 7.55 (dd, J = 8.1, 4.8 Hz, 1H) 8.48 (dt, J = 0.8, 2.0 Hz, 1H)

8.60 (dd, J = 4.8, 2.0 Hz, 1H) 8.65 (d, J = 2.4Hz, 1H) 8.89 (d, J = 2.4Hz, 1H) 8.94 (d, J = LO Hz, 1H)

9.06 (d, J = LO Hz, 1H) 9.34 (d, J = 2.0Hz, 1H) 12.09 (spread m, 1H)

UPLC-MS-DAD-ELSD: 279 (-) /... (M-H) (-) / ...; 281 (+) / ... = (M + H) (+) / ... (1 Cl present) (Tr = 0.52 min)

Example 14: Synthesis of 3- (morphol-4-yl) -6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-cipyridine 11:

In a microwave reactor of suitable size are introduced 50 mg of 10, 11.4 mg of tris (dibenzylideneacetone) dipalladium (0), 11.3 mg of 2-di-t-butylphosphino-2 ', 4', 6'-tri-i-propyl-1,1'-biphenyl, 49.9 mg of potassium tert-butoxide, 77.5 mg of morpholine and 2.5 ml of dioxane. The mixture is heated for 1 hour at 140 ^° C. After adding 2 ml of methanol, the reaction medium is poured into 10 ml of ethyl acetate. 500 mg of silica are then added, the mixture obtained is concentrated under reduced pressure in order to produce a solid deposit on a column. The product is purified by silica gel chromatography (25 g of silica) using a gradient of 3 to 10% methanol in dichloromethane to give 52 mg of crude product which is then purified by preparative HPLC to give 14.6 g. mg (23%) of 3- (morpholin-4-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 11.

1H NMR (400MHz, DMSO -? / 6)? Ppm: 3.20 (m, 4H) 3.84 (m, 4H) 7.53 (dd, J = 8.3, 4.9Hz, 1H) 8.34 (d, J = 2.9) Hz, 1H) 8.47 (partially masked m, 1H) 8.49 (d, J = 2.9Hz, 1H) 8.57 (dd, J = 4.9, 2.0Hz, 1H) 8.88 (d, J = 1Hz Hz, 1H) ) 8.96 (d, J = 1 Hz, 1H) 9.34 (d, J = 2.0Hz, 1H) 11.99 (m, spread 1H) UPLC-MS-DAD-ELSD: 330 (-) = (MH) ( -); 332 (+) = (M + H) (+) (Tr = 0.41 min)

Example 15: Synthesis of 3-hydroxy-2,2-dimethylpropyl 6- (pyrid-3-yl) -9H-pyrroloryl] -5,4-cHdipyridine-3-carboxylate 12:

In a microwave reactor of suitable size are introduced 100 mg of 5c, 2.5 g of 2,2-dimethyl-1-3-propanediol, and 13 mg of sodium hydride. The mixture is heated under microwave for 30 minutes at 160 ^° C. The solid is then solubilized in 80 ml of a mixture of water / AcOEt: 1/1. The organic phase is extracted, dried over magnesium sulfate, filtered and evaporated. The crude residue is then purified by chromatography on silica gel (15 g of silica) using a gradient of 2 to 5% methanol in dichloromethane. The fractions containing the expected product are combined and concentrated under reduced pressure to give 31 mg (25%) of 6- (pyridin-3-yl) -9H-pyrrolo [2,3-e: 5,4-c] dipyridine. 3-hydroxy-2,2-dimethylpropyl 3-carboxylate 12.

NMR (400 MHz, DMSO -? / 6) δ ppm 1.00 (s, 6H) 3.36 (d, J = 5.4 Hz, 2H) 4.15 (s, 2H) 4.71 (t, J = 5.4Hz, 1H NMR (400 MHz, DMSO? H) 7.55 (dd, J = 8.1, 4.7 Hz, 1H) 8.54 (dt, J = 8.1, 2.0 Hz, 1H) 8.60 (dd, J = 4.7, 2.0Hz, 1H) 9.08 (s, 1H) ) 9.13 (s, 1H) 9.18 (d, J = 2.4Hz, 1H) 9.30 (d, J = 2.4Hz, 1H) 9.40 (broad d, J = 2.0Hz, 1H) 12.78 (sgr, 1H) H) UPLC-MS-DAD-ELSD: 375 (-) = (M -) (-); 377 (+) = (M + H) (+) (Tr = 0.54 min)

Example 16: Synthesis of 2-r6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-c'ldipyridin-3-yllpropan-2-ol 13:

In a dry monocolon and under argon are introduced 130 mg of 5c and 7 ml of THF. The mixture is cooled to -20 ^° C., and then 0.710 ml of a solution of 3M methyl magnesium bromide in ethyl ether is added over 10 minutes. After stirring for 3 hours, 0.5 ml of methanol are added and the reaction medium is then hydrolysed with 25 ml of aqueous 10% ammonium chloride solution and 25 ml of water. The aqueous phase is extracted twice with 40 ml of ethyl acetate, dried over magnesium sulphate, filtered and concentrated under reduced pressure. The dry residue is then purified by chromatography on silica gel (25 g of silica) using a gradient of 3 to 10% of methanol in dichloromethane. The fractions containing the expected product are combined and concentrated under reduced pressure to give 94 mg (72%) of 2- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] '] dipyridin-3-yl] propan-2-ol 13 whose characteristics are as follows: 1H NMR (400MHz, DMSO -? / 6)? Ppm: 1.59 (s, 6H) 5.29 (s, 1H) 7.52 (dd, J = 7.8, 4.9Hz, 1H) 8.52 (dt, J = 7.8) , 2.0 Hz, 1H) 8.58 (dd, J = 4.9, 2.0Hz, 1H) 8.76 (d, J = 2.4Hz, 1H) 8.82 (d, J = 2.4Hz, 1H) 8.96 (d, J) = 0.8 Hz, 1H) 8.99 (d, J = 0.8Hz, 1H) 9.38 (d, J = 2.0Hz, 1H) 12.15 (brs, 1H) LC-MS-DAD-ELSD: 303 (-) ) = (MH); 305 (+) = (M + H) (+) (Tr = 2.15 min)

Example 17: Synthesis of 6- (pyrid-3-yl) -9H-pyrrolor 2,3-b: 5,4-cidipyridin-3-ylmethanol 14

To a mixture of 120 mg of 6-pyrid-3-yl-9H-pyrrolo [2,3-b: 5,4-c] dipyridine-3-carboxylic acid methyl ester (product described in US Pat. Step 2 of Example 30) in 3.5 ml of THF under argon is added in 5 minutes 0.6 ml of 1M lithium aluminum hydride in THF. After stirring for 2 hours, 0.2 ml of methanol are added to the reaction medium, which is then poured into a mixture of 100 ml of ethyl acetate and 100 ml of 1 M aqueous sodium tartrate-potassium solution. and stirred vigorously for 1 hour. The organic phase is extracted, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue is purified by chromatography on silica gel (15 g of silica) using a gradient of 0 to 10% methanol in ethyl acetate. The fractions containing the expected product are combined and concentrated under reduced pressure. The crude product obtained is then purified by semi-preparative HPLC to give 31.9 mg (30%) of [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] ] dipyridin-3-yl] methanol 14.

IH NMR (400 MHz, DMSO -? / 6) δ ppm: 4.71 (d, J = 5.6 Hz, 2H) 5.36 (t, J = 5.6 Hz, 1H) 7.53 (broad dd, J = 8.0, 4.8 Hz) , 1H) 8.52 (dt, J = 8.0, 2.0 Hz, 1H) 8.56 - 8.60 (m, 2H) 8.68 (d, J = 2.0Hz, 1H) 8.93 (d, J = 1.0Hz, 1H) ) 9.01 (d, J = LO Hz, 1H) 9.37 (broad d, = 2.0 Hz, 1H) 12.20 (bs, 1H) UPLC-MS-DAD-ELSD: 275 (-) = (MH) ( -); 277 (+) = (M + H) (+) (Tr = 0.30 min)

Example 18 Synthesis of 2-methylpropyl 6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-c'ldipyridine-3-carboxylate

2.5 mmol of 2-methylpropan-1-ol are charged into a microwave tube with 1 ml of THF, cooled with an ice-bath, and then 2.5 mmol of n-butyllithium is added. . 0.5 mmol of methyl ester 5c is added and the tube is sealed. The reaction medium is irradiated in the microwave oven for 30 minutes at 140 ^° C., then 2 ml of ethyl acetate are added. After stirring for 5 minutes at 25 ^° C., 2 ml of a saturated aqueous solution of potassium dihydrogenphosphate are added, the precipitate obtained is drained, washed with tetrahydrofuran and dried to give 124 mg (72%) of 6- ( 2-methylpropyl pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c'] dipyridine-3-carboxylate 15.

1H NMR (400MHz, DMSO -? / 6)? Ppm 1.05 (d, J = 6.6Hz, 6H) 2.11 (m, 1H) 4.17 (d, J = 6.6Hz, 2H) 7.54 (dd, J) = 7.8, 4.8 Hz, 1H) 8.54 (dt, J = 7.8, 1.7 Hz, 1H) 8.60 (dd, J = 4.8, 1.7 Hz, 1H) 9.07 (s, 1H) 9.12 (s, 1H) ) 9.17 (d, J = 2.1 Hz, 1H) 9.31 (d, J = 2.1Hz, 1H) 9.40 (d, J = 1Hz, 1H) 12.75 (s, 1H)

Example 19 Synthesis of 6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-c'ldipyridine-3-carboxylic acid 16:

In a microwave tube 0.66 mmol of methyl ester 5c is charged with 1 ml of methanol and 1 ml of tetrahydrofuran, 2 ml of 1N aqueous sodium hydroxide solution are added and the tube is sealed. The reaction medium is irradiated in the microwave oven for 30 minutes at 140 ^° C., then 2 ml of a 1N aqueous solution of hydrochloric acid is added. The precipitate obtained is filtered and dried to give 6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine-3-carboxylic acid quantitatively 16.

1H NMR (400MHz, DMSO -? / 6)? Ppm: 7.53 (dd, J = 7.9, 4.9Hz, 1H) 8.53 (dt, J = 7.9, 2.0Hz, 1H) 8.60 (dd, J = 4.9) , 2.0 Hz, 1H) 9.05 (d, J = LO Hz, 1H) 9.08 (d, J = LO Hz, 1H) 9.14 (d, J = 2.0Hz, 1H) 9.27 (d, J = 2.0) Hz, 1H) 9.39 (d, J = 2.0Hz, 1H) 11.5 (m very spread, 1H) LC-MS-DAD-ELSD: 289 (-) = (MH) (-); 291 (+) = (M + H) (+) (Tr = 1.11 min)

Example 20: Synthesis of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-cipyridine 19:

Step 1 :

In a three-necked 250 ml, 3.2 g of 5b and 90 ml of dimethylformamide are introduced. The mixture is stirred and then 847 mg of sodium hydride are added under argon. After two hours, 4.61 g of tosyl chloride in 10 ml of dimethylformamide are added. After stirring for two hours at room temperature, it is poured into 250 ml of a 10% sodium bicarbonate solution and 250 ml of water, extracted twice with 300 ml of ethyl acetate, and dried over. magnesium sulfate and filter. It is purified by chromatography on silica gel (dichloromethane / methanol gradient 100/0 to 95/5). 4.75 g (94%) of the intermediate 3-fluoro-6-pyridin-3-yl-9- (toluene-4-sulphonyl) -9H-pyrrolo [2,3-e] 5,4- c] dipyridine 17.

UPLC-MS-DAD-ELSD: 419 (+) = (M + Η) (+) (Tr = I, 19 min)

2nd step :

In a dry flask under an argon atmosphere, 0.73 ml of diisopropylamine is introduced into 20 ml of THF. The solution is cooled to -78 ^° C. and then 1.94 ml of n-butyllithium (2.5 M in hexane) is added. The mixture is stirred for 15 minutes and then 1.35 g of previously dissolved in 80 ml of tetrahydrofuran are introduced dropwise. After stirring for 2 hours at -78 ° C., 1.31 g of the diiodode previously dissolved in 5 ml of tetrahydrofuran are introduced dropwise. Stirred for 10 minutes. The reaction medium is poured into 250 ml of an ammonium chloride solution and extracted with 500 ml of ethyl acetate. The organic phase is washed with 200 ml of an aqueous solution of sodium thiosulfate and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure. 1.65 g (91%) of the expected compound 3-fluoro-4-iodo-6-pyridin-3-yl-9- (toluene-4-sulfonyl) -9H-pyrrolo [2,3-e: 5.4 Dipyridine 18 is thus obtained and the product is engaged in the subsequent steps without further purification.

UPLC-MS-DAD-ELSD: 545 (+) = (M + Η) (+) (Tr = I, 32 min) Step 3:

In a flask, 700 mg of 18 are introduced with 15 ml of methanol and 35 ml of tetrahydrofuran. An aqueous solution of lithium hydroxide (420 mg of LiORH ₂ O dissolved in 25 ml of water) is added. Stirred for 2 hours. 50 ml of water are added and the reaction medium is neutralized with 5 ml of a 2M aqueous hydrochloric acid solution. The precipitate is filtered and then dried. There is thus obtained 380 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 19.

1H NMR (400MHz, DMSO -? / 6)? Ppm 7.56 (dd, J = 8.0, 4.5Hz, 1H) 8.43 (dt, J = 8.0, 2.0Hz, 1H)

8.56 (s, 1H) 8.62 (dd, J = 4.5, 2.0 Hz, 1H) 9.10 (d, J = 8.0 Hz, 2H) 9.27 (d, J = 2.0Hz, 1H) 12.6 (metal,

I H)

LC-MS-DAD-ELSD: 391 (+) = (M + H) (+)

Example 21 to 31 (21a-21k):

GENERAL PROCEDURE FOR COUPLING SUZUKI IN POSITION 4

In a microwave reactor of suitable size, 100 mg (0.25 mmol) of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5 are introduced. , 4-c '] dipyridine 19, 0.75 mmol of a boronate 20a-k, 26.6 mg of tetrakis (triphenylphosphine) palladium (O), 125 mg of cesium carbonate, 2 ml of dioxane and 0.5 ml of water. The mixture is irradiated for 1 hour between 120 and 130 ^° C. The suspension obtained is taken up with water and ethyl acetate, the solid is drained on sintered glass (0.45 μm), washed with acetate. of ethyl and dried to give the expected compound 21a-k.

When the purity of the solid is less than 90%, or in cases where crystallization does not take place, the crude reaction product is purified by preparative HPLC (VP240 / 50mm NUCLEODUR 100-10 C18ec column) using an acetonitrile gradient. in water (Milli-Q + 0.07% TFA). The fractions containing the expected product are combined and concentrated under reduced pressure to give the expected compound 21a-k. The results of these experiments are compiled in Table 3.

Table 3

Example 32 Synthesis of 4-Cyclopropyl-3-fluoro-6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-c'ldipyridine

22:

In a microwave reactor of suitable size are introduced 100 mg of 19, 129.2 mg of (4,4,5,5-tetramethyl-1,3,2-dioxaborolan) cyclopropane, 26.6 mg of tetrakis ( triphenylphosphine) palladium (O), 81.6 mg of potassium phosphate, 2 ml of dioxane and 0.500 ml of water. The mixture is irradiated 1 hour at 150 ^° C. The suspension obtained is taken up with water and ethyl acetate, the solid is drained on frit (0.45 microns), washed with ethyl acetate and dried . 68 mg (87%) of pale yellow solid 4-cyclopropyl-3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 22 are obtained.

1H NMR (400MHz, DMSO -? / 6)? Ppm: 1.13 (m, 2H) 1.40 (m, 2H) 2.70 (m, 1H) 7.73 (dd, J = 7.8, 5.2Hz, 1H) 8.51 (d, J = 4.0 Hz, 1H) 8.70 (broad d, J = 5.2 Hz, 1H) 8.78 (broad d, J = 7.8 Hz, 1H) 8.88 (s, 1H) 9.08 (d, J) = 1.0 Hz, 1H) 9.46 (d, J = 1Hz, 1H) 12.46 (bs, 1H)

Example 33: Synthesis of 3-Fluoro-4- (morphol-4-yl) -6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridine; trifluoroacetic acid salt 23:

To a mixture of 100 mg of 19 and 28 mg of potassium tert-butoxide in 1 ml of dioxane is added a solution previously stirred under argon for 15 minutes of 37 mg of 9,9-dimethyl-4,5-bis ( diphenylphosphino) xanthene, 23.4 mg tris (dibenzylideneacetone) dipalladium and ImI anhydrous dioxane. 1 ml of dioxane is added to rinse glassware containing Xantphos / Pd (OAc) ₂ . 120 μL of morpholine are then added. The mixture obtained is irradiated in the microwave oven for one hour at 130 ^° C. The reaction medium is concentrated under reduced pressure and then purified by preparative HPLC (VP240 / 50mm column NUCLEODUR 100-10 C18ec) using an acetonitrile gradient in water (Milli-Q water supplemented with 0.07% trifluoroacetic acid). The fractions containing the expected product are combined and concentrated under reduced pressure to give 36 mg (30%) of yellow solid 3-fluoro-4- (morpholin-4-yl) -6- (pyridin-3-yl) -9H- pyrrolo [2,3-b: 5,4-c] dipyridine in the form of trifluoroacetic acid salt.

1H NMR (400MHz, DMSO -? / 6)? Ppm: 3.56 (m, 4H) 3.96 (m, 4H) 7.76 (br m, 1H) 8.37 (s, 1H) 8.50 (d, J = 6.0 Hz, 1H) 8.66 - 8.74 (m, 2H) 9.03 (s, 1H) 9.38 (s, 1H) 12.42 (bs, 1H)

Synthesis of 3-fluoro-6-pyrid-3-yl-9- (toluene-4-sulfonyl) -4-trimethylstannyl-9H-pyrrolor2,3-b: 5,4-cidipyridine 24

In a dry monocolon and under argon are introduced 2.14 ml of diisopropylamine in 60 ml of THF. The mixture is stirred and cooled to -78 ⁰ C before adding 5.73 ml of n-butyllithium. After stirring for 15 minutes, 4 g of compound 17 previously dissolved in 240 ml of THF are added. The reaction is stirred for 2 h and then 3.04 g of chloro (trimethyl) stannane in 20 ml of THF are added. After returning to 25 ^° C., the reaction medium is hydrolyzed with 250 ml of a 10% aqueous solution of ammonium chloride and 250 ml of water, the aqueous phase is then extracted twice with 300 ml of sodium acetate. 'ethyl. The combined organic phases are washed with a saturated aqueous solution of KF, dried over magnesium sulphate, filtered and concentrated under reduced pressure. The crude residue obtained is purified by chromatography on silica gel (600 g of silica) using a gradient of 1% to 6% of methanol in dichloromethane. The fractions containing the expected product are combined and concentrated under reduced pressure. 2.79 g of product are obtained, which are again purified by chromatography on silica gel (200 g of silica) using a gradient of 0% to 6% of methanol in dichloromethane, to give 1.3 g (22% ) 3-fluoro-6-pyridin-3-yl-9- (toluene-4-sulfonyl) -4-trimethylstannyl-9H-pyrrolo [2,3-b: 5,4-c] dipyridine 24.

UPLC-MS-DAD-ELSD: 583 (+) = (M + H) (+) (isotopic profile corresponding to a tin derivative) Tr (min) = 1.43

Example 34-36 (27a-27c)

GENERAL PROCEDURE FOR THE SYNTHESIS OF KETONE AND AMINE VIA THE TRIMETHYLSTANNYL DERIVATIVE IN 4 24

0.2 mmol of 3-fluoro-6-pyridin-3-yl-9- (toluene-4-sulfonyl) -4-trimethylstannyl-9H-pyrrolo [2] are introduced into a microwave reactor of suitable size. Dichlorobis (triphenylphosphine) palladium (II), 3 ml of toluene, 0.2 mmol of copper iodide, and 0.5 mmol of chloride 25a-c The mixture is irradiated for 1 hour between 110 and 120 ^° C. The reaction medium is hydrolyzed with 25 ml of water, then the aqueous phase is extracted twice with 50 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue obtained is purified by chromatography on silica gel (25 g of silica) using a gradient of 0% to 6% of methanol in dichloromethane. The tosylated intermediates 26a-c are thus obtained. The product 26a-c is taken up in 4 ml of a methanol-tetrahydrofuran mixture (1 to 1 by volume), then an aqueous solution of lithium hydroxide is added. After stirring for two hours, the reaction medium is neutralized with an aqueous ammonium chloride solution and extracted twice with 40 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residues are purified by chromatography on silica gel (25 g of silica, gradient of elution: dichloromethane-methanol 98/2 to 95/5). The products 27a-c obtained are described in Table 4.

Table 4

Example 37: Synthesis of 4-Chloro-3-fluoro-6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-c'ldipyridine 29:

Step 1

In a dry monocolon and under argon are introduced 105 .mu.l of diisopropylamine in 3 ml of THF. The mixture is stirred and cooled to -78 ⁰ C before addition of 280 .mu.l of N-butyllitium. After stirring for 15 minutes, 210 mg of 3-fluoro-6-pyridin-3-yl-9- (toluene-4-sulfonyl) -9H-pyrrolo [2,3-e: 5,4-c] dipyridine 17 in 4 ml of THF are added. The reaction is stirred for 2 h and then 191 mg of toluenesulfonyl chloride in 1 ml of THF are added. After 1 hour of agitation, the medium The reaction mixture is hydrolyzed with 50 ml of 10% aqueous ammonium chloride solution and 50 ml of water, and then the aqueous phase is extracted twice with 50 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue obtained is purified by chromatography on silica gel (25 g of silica, using a gradient of 10% to 66% of ethyl acetate in dichloromethane The fractions containing the expected product are combined and concentrated under reduced pressure to give 81 mg (35%) of 3-Fluoro-4-chloro-6-pyridin-3-yl-9- (toluene-4-sulfonyl) -9H-pyrrolo [2,3-e: 5,4-c] ^/ ] dipyridine 28.

LC-MS-DAD-ELSD: 453 (+) = (M + Η) (+) (isotopic profile corresponding to a chlorinated derivative) Tr (min) = 4.53

2nd step

A single-are introduced 80 mg 3-fluoro-4-chloro-6-pyridin-3-yl-9- (toluene-4-sulfonyl) - 9H-pyrrolo [2,3-b: 5,4-c ^/] dipyridine, 2 ml of methanol, 2 ml of THF and 41 mg of lithium hydroxide dissolved in 0.500 ml of water. The reaction mixture is stirred overnight at 25 ^° C. and the methanol and THF are then evaporated under reduced pressure. . The crude residue obtained is taken up in 5 ml of water and 2 ml of a 10% aqueous solution of ammonium chloride, triturated, filtered and then purified by preparative HPLC (Macherey-Nagel column 250 × 40 mm reverse phase Cl 8 Nucleoside 10 μl). ). Elution according to the gradient (acetonitrile at 0.07% TFA and H ₂ O at 0.07% TFA). The fractions containing the expected compound are combined, the acetonitrile is evaporated under reduced pressure, the water is removed by freeze-drying, to give 6 mg of 4-chloro-3-fluoro-6- (pyridin-3-yl) -9H pyrrolo [2,3-b: 5,4-c] dipyridine 29.

1H NMR (400MHz, DMSO -? / 6)? Ppm: 7.54 (dd, J = 8.1, 4.8Hz, 1H) 8.52 (dt, J = 8.1, 1.8Hz, 1H)

8.60 (dd, J = 4.8, 1.8 Hz, 1H) 8.79 (d, J = 2.4 Hz, 1H) 8.80 (d, J = LO Hz, 1H) 9.13 (d, J = LO Hz, 1H)

9.36 (d, J = 1.8 Hz, 1H) 12.23 (spread m, 1H)

UPLC-MS-DAD-ELSD: 297 / ... (-) = (M-H) / ... (-); 299 (+) /...= (M + H) / ... (+) (I Cl present) (Tr = 2.74 min)

Example 38: Synthesis of 4-methyl-3-fluoro-6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-idipyridine 31

In a dry monocolon and under argon are introduced 106 .mu.l of diisopropylamine in 3 ml of THF. The mixture is stirred and cooled to -78 ⁰ C before addition of 280 .mu.l of N-butyllitium. After stirring for 15 minutes, 210 mg of 3-fluoro-6-pyridin-3-yl-9- (toluene-4-sulfonyl) -9H-pyrrolo [2,3-e: 5,4-c] dipyridine 17 in 4 ml of THF are added. The reaction is stirred for 2 h and then 142.5 mg of iodomethane in 1 ml of THF is added. After stirring for 1 hour, the reaction medium is hydrolyzed with 50 ml of aqueous 10% ammonium chloride solution and 50 ml of water, and then the aqueous phase is extracted twice with 50 ml of ethyl acetate. . The combined organic phases are dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue obtained is purified by chromatography on silica gel (25 g of silica, using a gradient of 10% to 66% of ethyl acetate in dichloromethane The fractions containing the expected product are combined and concentrated under reduced pressure The 60 mg obtained are purified by semi-preparative HPLC (Kromasil Cl 8 column 5μm, 2 × 25cm), eluting at 18 ml / min with a mixture of 70% acetonitrile and 30% water. 28%) of 3-Fluoro-4-methyl-6-pyridin-3-yl-9- (toluene-4-sulfonyl) -9H-pyrrolo [2,3-e: 5,4-c] dipyridine are obtained .

LC-MS-DAD-ELSD: 433 (+) = (M + Η) (+) Tr (min) = 4.78

2nd step

16 mg of 3-fluoro-4-methyl-6-pyridin-3-yl-9- (toluene-4-sulfonyl) -9H-pyrrolo [2,3-e] 5,4-c are introduced into a monocolumn. dipyridine, 1 ml of methanol, 0.500 ml THF and 16 mg of lithium hydroxide dissolved in 0.500 ml of water. The reaction mixture is heated for one hour at 45 ^° C., and then a 10% aqueous solution of ammonium chloride is added dropwise until a precipitate forms. After wringing off the precipitate and washing three times with 5 ml of distilled water, 5 mg of 4-methyl-3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5 are obtained. 4-c '] dipyridme whose characteristics are as follows:

IH NMR (400 MHz, DMSO - </ 6) δ ppm 2.91 (d, J = 1.5 Hz, 3H) 7.52 (dd, J = 8.1, 4.6 Hz, 1H) 8.53 - 8.61 (m, 3H) 8.71 (s, 1H) 9.05 (s, 1H) 9.41 (d, J = 2.2Hz, 1H) 12.23 (spread m, 1H)

Synthesis of 6-methoxy-9H-pyrrolor2,3-b: 5,4-c'ldipyridine 35:

Step 1

In a dry monocolon and under argon are introduced 10.5 ml of diisopropylamine in 40 ml of THF. The mixture is stirred and cooled to -78 ⁰ C, then 29.73 ml of N-butyllitium are added dropwise in 45 minutes, then 10 g of 2,5-dichloropyridine solubilized in 170 ml of THF in 20 minutes. The medium turns yellow and then browns. After stirring for 2 h, 17.5 g of chloro (trimethyl) stannane are added in solution in THF in 20 minutes at -78 ^° C. and then allowed to return to -10 ^° C. overnight. The reaction medium is hydrolyzed with 1 liter of ammonium chloride solution and 300 ml of water, and then the aqueous phase is extracted with ethyl acetate. The organic phase is dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue obtained is purified by chromatography on silica gel using a gradient of 0% to 25% ethyl acetate in heptane. The fractions containing the expected product are combined and concentrated under reduced pressure to give 18 g of 2,5-dichloro-4-trimethylstanannanyl-pyridine 32 as a white solid. LC-MS-DAD-ELSD: 309 (+) = (M + H) (+) (isotopic profile corresponding to a tin derivative) Tr (min) = 5.09

2nd step

In a microwave reactor of suitable size are introduced 220 mg of 2-amino-3-iodopyridine, 311 mg of 2,5-dichloro-4-trimethylstanannanyl-pyridine 32, 80.89 mg of tetrakis (triphenylphosphine) palladium ( 0), 40 mg of copper iodide and 3 ml of dioxane. The reaction medium is irradiated for 1 hour at 125 ^° C. and then hydrolyzed with 75 ml of a 10% aqueous solution of sodium bicarbonate and 5 ml of water. The aqueous phase is extracted twice with 50 ml of ethyl acetate, the combined organic phases are then dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue obtained is purified by chromatography on silica gel (70 g of silica) using a gradient of 0% to 5% of methanol in ethyl acetate. The fractions containing the expected product are combined and concentrated under reduced pressure to give 133 mg of 2 ', 5'-Dichloro [3,4'] bipyridinyl-2-ylamine 33. LC-MS-DAD-ELSD: 239.9 (+) = (M + H) (+) (isotopic profile corresponding to a dichlorinated derivative) Tr (min) = 1.94

Step 3

1 g of 2 ', 5'-dichloro [3,4'] bipyridinyl-2-ylamine, 10 ml of methanol and 202.5 mg of sodium methoxide are introduced into a microwave reactor of suitable size. The mixture is irradiated 3 times 1 hour at 100 ⁰ C, then the suspension obtained is filtered and washed with dichloromethane. This product is purified by preparative HPLC (acid eluent). The fractions containing the expected product are combined and concentrated under reduced pressure to give 2.3 g of 5'-chloro-2'-methoxy- [3,4 '] bipyridinyl-2-ylamine 34 as a white solid.

Step 4

To a yellow suspension of 100 mg of 5'-chloro-2'-methoxy- [3,4 '] bipyridinyl-2-ylamine ethyl ester, 66.61 mg of potassium tertbutoxide and 5 ml of dioxane under argon, an orange-brown solution, previously stirred under argon, is added for 10 minutes of 25.86 mg of (R) - (-) - 1- [- ((S) -2- (dicyclohexylphosphino) ferrocenyl] ethyl-di-butyl-phosphine, 9 , 52 mg of palladium (II) acetate and 1 ml of anhydrous dioxane. 1 ml of dioxane is added to rinse the glassware containing the preparation Josiphos / Pd (OAc) ₂ The reaction medium is then irradiated for 1 hour at 150 ^° C. The insoluble suspension obtained is separated by filtration, washed with dichloromethane, then the filtrate is concentrated under reduced pressure. The crude residue is purified by acid preparative HPLC (240/50 mm NUCLEODUR 100-10 C18ec VP column) using a gradient of acetonitrile in Milli-Q water at 0.07% trifluoroacetic acid. The fractions containing the expected product are combined and concentrated under reduced pressure to give 70 mg of 6-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridine beige solid as an acid salt. trifluoroacetic

LC-MS-DAD-ELSD: 200 (+) = (M + H) (+) Tr (min) = 2.45

1H NMR (400MHz, DMSO -? / 6)? Ppm: 3.93 (s, 3H) 7.24 (dd, J = 7.8, 4.9Hz, 1H) 7.63 (s, 1H)

8.48 (s, 1H) 8.56 (dd, J = 4.9, 1.7Hz, 1H) 8.63 (dd, J = 7.8, 1.7Hz, 1H) 11.84 (brs, 1H)

Example 39 to 41 (39a-39c):

Triflate preparation and Suzuki coupling:

Step 1

To a solution of 305 mg of 6-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridine in 7.5 ml of acetic acid is added 1.5 ml of a solution. 37% hydrochloric acid. The mixture is heated in the microwave oven for 3 hours at 150 ^° C., the insoluble matter formed is drained and washed with diethyl ether to give 312 mg of 9H-dipyrido [2,3-b: 4 ', 3' pyrrol-6-ol 36.

UPLC-MS-DAD-ELSD: 186 (+) = (M + H) (+) Tr (min) = 0.32

2nd step

To a suspension of 280 mg of 9H-dipyrido [2,3-b: 4 ', 3'-d] pyrrol-6-ol 36 in 8 ml of pyridine is added 1 ml of trifluoromethanesulfonic anhydride, then 0.5 ml after stirring for 1 hour at 25 ^° C. The reaction medium is stirred for 1 night and then concentrated under reduced pressure. The residue is taken up with dichloromethane, the organic phase obtained is washed with a saturated aqueous solution of sodium bicarbonate and then concentrated under reduced pressure. The brown solid obtained is purified by chromatography on silica gel (30 g of silica) using a gradient of 0% to 100% of ethyl acetate in heptane. The fractions containing the expected product are combined and concentrated under reduced pressure to give 305 mg of trifluoromethanesulfonate of 9 - [(trifluoromethyl) sulfonyl] - 9H-pyrrolo [2,3-b: 5,4-c ^/] dipyridin-6- yle, as a beige solid 37.

UPLC-MS-DAD-ELSD: 450 (+) = (M + Η) (+) Tr (min) = 1.39

Step 3

0.1 mmol of 9 - [(trifluoromethyl) sulfonyl] -9H-pyrrolo [2,3-di-5,4-c] dipyridin-6-yl trifluoromethanesulfonate are introduced into a suitable sized microwave reactor. , 5 μmol of 1,1-bis (diphenylphosphino) ferro-dichloro palladium (II), 0.3 mmol of cesium carbonate, 2 ml of dioxane and 0.500 ml of water and 0.15 mmol of the boronic derivative 38a-c. The mixture obtained is irradiated for 30 minutes at 120 ^° C. and then taken up in ethyl acetate and with water. After settling, separation and washing of the two phases, the organic phases are combined and concentrated under reduced pressure. The crude residue is triturated in acetonitrile, and the suspended solid thus obtained is drained under vacuum and washed with ethyl ether to give the expected compounds 39a-c (see Table 5).

Table 5

Synthesis of 6-Methylsulfanyl-9H-pyrrolor2,3-b: 5,4-cispyridine 41:

A mixture of 740 mg of 2 ', 5'-Dichloro [3,4'] bipyridinyl-2-ylamine (product described in Step 2 of Example 43) and 216 mg of sodium methanethiolate in 12 ml of DMF is irradiated in the microwave oven five times for 1 hour at 100 ^° C. The brown suspension obtained is filtered, washed with ethyl acetate, and the filtrate concentrated under reduced pressure. The crude residue is taken up in dimethylsulfoxide and then purified by basic preparative HPLC (VP 240/50 mm NUCLEODUR 100-10 C18ec column) using a gradient of acetonitrile in water (Milli-Q water - added 0.07 % trifluoroacetic acid). The fractions containing the expected product are combined and concentrated under reduced pressure to give 495 mg of 5'-chloro-2'-methylsulfanyl- [3,4 '] bipyridinyl-2-ylamine 40 as a brown solid.

LC-MS-DAD-ELSD: 251 (+) = (M + H) (+) (isotopic profile corresponding to a chlorinated derivative) Tr (min) = 2.44 Step 2

To a suspension of 450 mg of 5'-chloro-2'-methylsulfanyl- [3,4 '] bipyridinyl-2-ylamine 40, 177.9 mg of potassium tertbutoxide and 10 ml of dioxane under argon, a solution is added. orange-brown previously stirred under argon for 10 minutes of 69 mg of (R) - (-) - 1 - [(S) -2- (dicyclohexylphosphino) ferrocenyl] ethyl-di-tert-butylphosphine, 25.4 mg of palladium ( II) acetate and 2 ml of anhydrous dioxane. 2 ml of dioxane are added to rinse the glassware containing the preparation Josiphos / Pd (OAc) ₂ The reaction medium is then irradiated for 2 hours at 150 ^° C. The insoluble suspension obtained is separated by filtration, the filtrate is taken up with dichloromethane and then washed with water. The organic phase is concentrated under reduced pressure, the crude residue thus obtained is solubilized in dimethylsulfoxide and purified by basic preparative HPLC (240/50 mm NUCLEODUR 100-10 C18ec VP column) using a gradient of acetonitrile in water ( Milli-Q water - supplemented with 0.07% trifluoroacetic acid). The fractions containing the expected product are combined and concentrated under reduced pressure to give 287 mg of 6-methylsulfanyl-9H-pyrrolo [2,3-b: 5,4-c '] dipyridine beige solid 41, the characteristics of which are as follows:

IH NMR (400MHz, DMSO -? / 6) δ ppm: 2.60 (s, 3H) 7.28 (dd, J = 7.8, 4.9Hz, 1H) 8.11 (d, J = 1.5Hz, 1H) 8.57 (dd , J = 4.9, 1.5 Hz, 1H) 8.65 (dd, J = 7.8, 1.5Hz, 1H) 8.78 (d, J = 1.5Hz, 1H) 11.96 (spread m, 1H)

Example 42: Synthesis of 6- (5-Fluoro-ryyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-c'ldipyridine 42:

60 mg of 6-methylsulfanyl-9H-pyrrolo [2,3-b: 5,4-c] dipyridine 41, 78.5 mg of 5-fluoropyridine-acid are introduced into a microwave reactor of suitable size. 3-boronic acid, 150 mg of copper thiophene-2-carboxylate, 32.2 mg of tetrakis (triphenylphosphine) palladium (0) and 76.7 mg of zinc acetate. Before adding 3 ml of DMF under argon, the air present in the reactor is removed under vacuum and replaced with argon. The mixture thus obtained is irradiated 3 times for 1 hour at 150 ^° C., then taken up with ethyl acetate and an aqueous solution of sodium bicarbonate, and filtered through a 0.42 μm and 0.22 μm membrane. The organic phase is concentrated in vacuo, the yellow oil obtained is purified by acidic preparative HPLC (VP column 240/50 mm NUCLEODUR 100-10 C18ec) using a gradient of acetonitrile supplemented with 0.07% of trifluoroacetic acid in Milli-Q water supplemented with 0.07% trifluoroacetic acid. The fractions containing the expected product are combined and concentrated under reduced pressure. The residue is repurified to give 3.5 mg (5%) of 6- (5-fluoro-pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine, in the form of of beige solid 42.

1H NMR (400MHz, DMSO -? / 6)? Ppm: 7.38 (dd, J = 7.8, 4.9Hz, 1H) 8.41 (ddd, J = 10.3, 2.4, 1.5Hz, 1H) 8.60 (d, J = 2.4 Hz, 1H) 8.64 (dd, J = 4.9, 1.7Hz, 1H) 8.71 (dd, J = 7.8, 1.7Hz, 1H) 9.02 (s, 1H) 9.04 (s, 1H) 9.28 ( s wide, 1H) 12.36 (wide, 1H)

Example 43 (45) and Example 44 (46):

Synthesis of N- [4- (3-methoxy-6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-di-dipyridin-4-yl] phenyl} -methanesulfonamide 46:

Step 1 :

In a tricolor of 150 ml, 0.5 g of 5 g and 12 ml of dimethylformamide are introduced. The mixture is stirred and then 126 mg of sodium hydride are added under argon. After two hours, 690 mg of tosyl chloride in 2 ml of dimethylformamide are added. After stirring for two hours at room temperature, poured into 100 mL of 10% sodium bicarbonate solution and 100 mL of water, extracted with 150 mL of ethyl acetate, dried over magnesium sulfate and filtered. It is purified by chromatography on silica gel (70 g of gradient silica dichloromethane / methanol 100/0 to 95/5). 721 mg (93%) of the intermediate 3-methoxy-6-pyridin-3-yl-9- (toluene-4-sulphonyl) -9H-pyrrolo [2,3-e: 5,4-c] are obtained dipyridine 43.

2nd step :

In a dry flask under an argon atmosphere, 0.31 ml of diisopropylamine is introduced into 10 ml of THF. The solution is cooled to -78 ^° C. and then 1.06 ml of n-butyllithium (2.5 M in hexane) is added. Stir 15 minutes and then dropwise introduced 600 mg of 43 previously dissolved in 40 mL of tetrahydrofuran. After stirring for 2 hours at -78 ° C., 566 mg of diiododeproduced beforehand in 5 ml of tetrahydrofuran are introduced dropwise. Stirred for 10 minutes. The reaction medium is poured into 250 ml of an ammonium chloride solution and extracted with 500 ml of ethyl acetate. The organic phase is washed with 200 ml of an aqueous solution of sodium thiosulfate and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure. The residue is purified by chromatography on silica gel (90 g of gradient silica dichloromethane / methanol 100/0 to 95/5) to give 270 mg (35%) of the expected compound 3-methoxy-4-iodo-6-pyridine -3-yl-9- (toluene-4-sulphonyl) -9H-pyrrolo [2,3-e: 5,4-c] dipyridine 44.

Step 3:

In a flask, 250 mg of 44 are added with 6 ml of methanol and 10 ml of tetrahydrofuran. An aqueous solution of lithium hydroxide (194 mg of LiOΗ · ₂ O dissolved in 5 ml of water) is added. Stirred for 2 hours. 10 ml of water are added and the reaction medium is neutralized with 4 ml of a 2M aqueous hydrochloric acid solution. The precipitate is filtered and then dried. There is thus obtained 107 mg of 3-methoxy-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 45.

Step 4:

In a microwave reactor of suitable size are introduced 100 mg (0.25 mmol) of 3-methoxy-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5 , 4-c '] dipyridine 46, 0.75 mmol of boronate 20b, 28 mg of tetrakis (triphenylphosphine) palladium (O), 121 mg of cesium carbonate, 2 ml of dioxane and 0.7 ml of water. The mixture is irradiated for 1 hour at 120. 1 ml of methanol is added, then the mixture is poured into water (25 ml) and ethyl acetate (50 ml), the phases are separated and the aqueous phase is dissolved. again extracted with 50 mL of ethyl acetate. The combined organic phases are dried over magnesium sulphate, filtered and then concentrated under reduced pressure. The residue is purified by chromatography on silica gel (30 g of dichloromethane / methanol gradient silica 100/0 to 90/10), 68 mg (61%) of the expected compound N- [4- (3-methoxy-6) are obtained. - (Pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-4-yl] phenyl} -methanesulfonamide 46. 1H NMR (400MHz, DMSO -? / 6) δ ppm: 3.10 (s, 3H) 3.87 (s, 3H) 7.42 (partially masked dd, J = 8.0.4.9Hz, 1H) 7.45 (d, J) = 8.0 Hz, 2H) 7.57 (m, 3H) 8.09 (dt, J = 8.0, 2.0Hz, 1H) 8.52 (dd, J = 4.9, 2.0Hz, 1H) 8.57 (s, 1H) 8.93 ( d, J = 2.0Hz, 1H) 8.98 (s, 1H) 10.14 (extended m, 1H) 12.20 (bs, 1H) UPLC - SQD: Retention time Tr (min) = 0.53; MH + = 446 +; MH + = 444 -; Purity: 98%

Method of synthesis of comparatives (not claimed):

Synthesis of the comparative molecule 3-methoxy-6- (pyrid-3-yl) -9H-pyrrolor2,3-c: 5,4-c'ldipyridme 51:

Step 1 synthesis of 47:

1.2 ml of diisopropylamine and 5 ml of tetrahydrofuran are introduced into a dry flask under an argon atmosphere equipped with magnetic stirring. The solution was cooled to -78 ° C and then 3.24 mL of n-butyllithium (2.5 M in hexane) was added. After stirring for 15 minutes, 1.47 g of 1, previously dissolved in 20 ml of tetrahydrofuran, are added. After stirring for 2 hours, 2.15 g of dissolved diiodine in 2.5 ml of THF are added. It is stirred for 1 hour at -78 ° C. The reaction medium is hydrolyzed with 120 ml of a solution of 10% ammonium chloride and 30 ml of water. Extracted twice with 50 ml of ethyl acetate, the combined organic phases are washed with an aqueous solution of sodium thiosulfate, then dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. 2.25 g of a crude product are obtained which is purified by chromatography on silica gel using a gradient of heptane and ethyl acetate eluent (from 100/0 to 60/40 by volume). 1.58 (66%) g of 5-chloro-4-iodo-2- (3'-pyridinyl) -pyridine 47 is thus obtained.

LC-MS-DAD-ELSD: 316.89 (+) = (M + H) (+) Tr (min) = 3.44

Step 2 synthesis of 49: In a monocolon 1.0 g of 5-amino-2-methoxypyridine is charged and dissolved in 40 ml of dioxane. 1.79 g of di-tert-butyldicarbonate are added and the mixture is refluxed overnight. After cooling, the solvent is evaporated off under reduced pressure and the residue is purified by chromatography on silica gel using a gradient of heptane and ethyl acetate eluent (from 90/10 to 70/30 by volume). 1.58 g of compound 48 (97%) is obtained

In a dry monocolon and under argon, a solution of 4 mmol of 48 in anhydrous tetrahydrofuran (20 ml) is introduced by syringe. It is cooled to -78 ° C. and 10 mmol of tert-butyllithium (1.5 M in pentane) are then added over 15 minutes. The temperature is allowed to rise to -10 ^° C. and left stirring for 3 hours. The reaction mixture is again cooled to -78 ° C and then a solution of 6 mmol of trimethyltin chloride in 4 mL of anhydrous tetrahydrofuran is added. The reaction mixture is then poured onto an aqueous solution of ammonium chloride which is extracted with ethyl acetate. The organic phase is dried over magnesium sulfate and concentrated under reduced pressure. The crude is purified by chromatography on silica gel using a heptane / ethyl acetate eluent gradient (from 95/50 to 70/30 by volume). 1.01 g (65%) of compound 49 is obtained.

LC-MS-DAD-ELSD: 389 (+) = (M + H) (+) (isotopic profile corresponding to a tin derivative) Tr (min) = 4.69

Step 3 synthesis of 50:

In a 5 ml microwave reactor are introduced 453 mg (1.43 mmol) of 47, 554 mg (1.43 mmol) of the tin derivative 49, 165 mg of tetrakis (triphenylphosphine) palladium (O), 81 mg of copper iodide and 3.5 ml of dioxane. The mixture is irradiated for 1 hour at 150 ^° C. After cooling the mixture is poured into an aqueous solution of sodium bicarbonate (55 mL) and ethyl acetate (50 mL), the phases are separated and the aqueous phase is again extracted with 50 mL of ethyl acetate. The combined organic phases are dried over magnesium sulphate, filtered and then concentrated under reduced pressure. The residue is purified by chromatography on silica gel (30 g of gradient silica heptane / ethyl acetate 1/1 with pure ethyl acetate), 367 mg (62%) of the expected compound is obtained.

LC-MS-DAD-ELSD: 413 (+) = (M + H) (+) Tr (min) = 3.59

The product is redissolved in 10 mL of methanol and then 50 mL of 4M hydrochloric acid in dioxane is added. After two hours the solvents are evaporated, the residue is dissolved in 100 ml of ethyl acetate and this phase is washed with an aqueous solution of sodium bicarbonate (100 mL). The organic phase is dried over magnesium sulfate and concentrated under reduced pressure. Compound 50 is obtained quantitatively and can be used without further purification.

LC-MS-DAD-ELSD: 313 (+) = (M + H) (+) Tr (min) = 2.60

Step 4 summary of 51:

Product 50 (400 mg, 1.28 mmol) is loaded into a 20 mL microwavable tube with 58 mg (0.064 mmol) of tris (dibenzylideneacetone) dipalladium, 55 mg (0.14 mmol) of 2-dicyclohexylphosphino- 2- (N, N-dimethylamino) biphenyl and 1.8 mmol of potassium tert-butoxide. The tube is sealed and then placed under an argon atmosphere, then 7 ml of 1,4-dioxane are added. The mixture is heated in the microwaves for 1 hour at 130 ^° C. After cooling, the reaction mixture is poured into 50 ml of a solution of sodium bicarbonate, extracted twice with 50 ml of ethyl acetate, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. The residue is purified by chromatography on silica gel (30 g of gradient silica ethyl acetate / methanol 100/0 to 90/10), 261 mg (74%) of the compound 3-methoxy-6- (pyridine) is obtained. 3-yl) -9H-pyrrolo [2,3-c: 5,4-c '] dipyridine expected 51.

LC-MS-DAD-ELSD: 275 (-) = (M-H) (-) Tr (min) = 2.11

Synthesis of the comparative molecule 3- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-b'ldipyridine 56:

Step 1 :

In a 5 ml microwave tube, 0.52 g of 5-bromo-2-fluoropyridine, 646 mg of 3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan) are introduced under argon. -2-yl) pyridine, 173 mg tetrakis (triphenylphosphine) palladium (O) and 1.46 g of cesium carbonate and 3.8 ml of 1,4-dioxane and 0.2 ml of water. We microwave heating for 1 hour at 125 ^° C. After cooling, the reaction mixture is poured into 50 ml of a solution of 10% sodium bicarbonate and 25 ml of water, extracted twice with 60 ml of water. ethyl acetate, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. 552 mg of a crude product which is purified by chromatography on silica gel, eluting with a mixture of heptane and ethyl acetate (gradient 100/0 to 60/40 by volume), are obtained thus 220 mg (42%) of 2-fluoro-5- (3'-pyridinyl) pyridine 52.

LC-MS-DAD-ELSD: 175 (+) = (M + H) (+) Tr (min) = 1.84

2nd step :

1.23 ml of diisopropylamine and 1 ml of tetrahydrofuran are introduced into a dry flask under an argon atmosphere equipped with magnetic stirring. The solution was cooled to -78 ° C and then 0.63 mL of n-butyllithium (2.5 M in hexane) was added. After stirring for 15 minutes, 220 mg of 52 previously dissolved in 3 ml of tetrahydrofuran are added. After stirring for 1 hour, 417 mg of diiodine dissolved in 1 mL of THF are added. It is stirred for 1 hour at -78 ° C. The reaction medium is hydrolyzed with 50 ml of a solution of 10% ammonium chloride and 10 ml of water. Extracted twice with 50 ml of ethyl acetate, the combined organic phases are washed with an aqueous solution of sodium thiosulfate, then dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. The residue is purified by chromatography on silica gel using a heptane / ethyl acetate eluent gradient (from 95/5 to 75/25 by volume), thus obtaining 258 mg (68%) of 2 fluoro-3-iodo-5- (3'-pyridinyl) -pyridine 53.

LC-MS-DAD-ELSD: 301 (+) = (M + H) (+) Tr (min) = 3.13

Step 3:

In a microwave reactor 5 ml are introduced 250 mg (0.83 mmol) of 2-fluoro-3-iodo-5- (3'-pyridinyl) -pyridme 53, 278 mg (0.91 mmol) of the boronate 54.96 mg of tetrakis (triphenylphosphine) palladium (O), 543 mg of cesium carbonate, 2.5 ml of dioxane and 0.3 ml of water. The mixture is irradiated for 1 hour at 120 ° C. After cooling, the reaction mixture is poured into 40 ml of a solution of 10% sodium bicarbonate and 5 ml of water, extracted twice with 50 ml of sodium acetate. ethyl, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. 289 mg of a crude product which is purified by chromatography on silica gel (30 g of gradient silica ethyl acetate / methanol 100/0 to 90/10), thus obtaining 202 mg (59%) of 55.

LC-MS-DAD-ELSD: 351 (+) = (M + H) (+) Tr (min) = 2.68 Step 4:

In a microwave reactor 5 ml are introduced 175 mg of 55 previously ground with 2.5 g of pyridinium hydrochloride. The tube is sealed and the powders are heated under microwaves for 30 minutes at 220 ^° C. After cooling, the solid is dissolved in ethyl acetate and this phase is then washed with an aqueous solution of sodium bicarbonate. After drying and evaporation of the solvent the residue is purified by preparative HPLC (Chiralcel OD-I phase 20 μm) to give 8 mg (6.5%) of the compound 3- (pyridin-3-yl) -9H-pyrrolo [2,3 -b: 5,4-b '] dipyridine expected 56.

LC-MS-DAD-ELSD: 247 (+) = (M + H) (+) Tr (min) = 2.14

Example 45: 1-Chloro-N- {4-fluoro-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b] -5,4-di-dipyridin-4-yl] phenylmethanesulfonamide

Step 1: 4- {3-Fluoro-9 - [(4-methylphenyl) sulfonyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 4-yl} aniline

330 mg of 3-fluoro-4-iodo-6-pyridin-3-yl-9- (toluene-4-sulfonyl) -9H-pyrrolo [2,3-a] 5,4-c are placed in a reactor. ] dipyridine 18, 398 mg of 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) aniline, 70 mg of tetrakis (triphenylphosphine) palladium (0), 296 mg of carbonate of cesium in 8.5 ml of 1,4-dioxane and 1.5 ml of water, sealed the tube and subjected to microwave irradiation at 125 ⁰ C for 1 h. 200 ml of water are added to the reaction medium and this is then extracted twice with 250 ml of ethyl acetate. The combined organic phases are concentrated to dryness under reduced pressure. The residue is purified by chromatography on a silica column, eluting with a 100: 0 to 97: 3 dichloromethane: methanol mixture to give 793 mg of 4- {3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6- (Pyridin-3-yl) -9Η-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl} aniline 57.

UPLC-MS-DAD-ELSD (LS): Tr (min) = 1.25; (M + H) (+): 510 (+)

Step 2: 1-Chloro-N- (4- {3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5, 4-C '] dipyridin-4-yl} phenyl) methanesulfonamide

In a reactor, 4- {3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5.4 [α] Dipyridin-4-yl} aniline 57 in 6 ml of tetrahydrofuran and 3 ml of dichloromethane, 83 μl of triethylamine and then 35 mg of chloromethanesulfonyl chloride, seal the tube, subjected to microwave irradiation for 20 minutes at 100 ° ^C. C. 35 mg of chloromethanesulfonyl chloride and 83 μl of triethylamine are again added and the reaction mixture is subjected again to microwave irradiation for 30 min at 110 ^° C. 300 ml of water are added to the reaction mixture and then is extracted with 2 times 300 ml of ethyl acetate. The combined organic phases are concentrated to dryness under reduced pressure.

The reaction medium is diluted with 5 ml of DMSO and purified by preparative HPLC, inverted phase in an acidic medium, eluting with a gradient of the 0.07% trifluoroacetic acid: acetonitrile mixture containing 0.07% trifluoroacetic acid for give 34 mg of 1-chloro-N- (4- {3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b] 4-c '] dipyridin-4-yl} phenyl) methanesulfonamide 58 as trifluoroacetic acid salt and white lyophilizate.

UPLC-MS-DAD-ELSD (LS): Tr (min) = 1.29; (M + H) (+): 622 (+) / ... (presence of a chlorine atom).

Step 3: 1-Chloro-N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} methanesulfonamide 59

34 mg of 1-chloro-N- (4- {3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6- (pyridin-3-yl) -9H-pyrrolo [2] are placed in a flask, 3-b: 5,4-c '] dipyridin-4-yl} phenyl) methanesulfonamide 58 in 1 ml of tetrahydrofuran and then 6.88 mg of lithium hydroxide monohydrate dissolved in 0.11 ml of water. The reaction mixture is stirred for 18 hours at room temperature and then concentrated to dryness under reduced pressure. The residue is diluted with 5 ml of DMSO and purified by preparative HPLC, reverse phase in an acidic medium, eluting with a 0.07% trifluoroacetic acid: 0.07% trifluoroacetic acid acetonitrile gradient to give 13 mg. 1-chloro-N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} methanesulfonamide 59 in the form of trifluoroacetic acid salt and white lyophilisate.

UPLC-MS-DAD-ELSD: Tr (min) = 0.66; [M + H] +: m / z 468. 1H NMR (400MHz, DMSO-d6) δ ppm: 5.20 (s, 2H) 7.52 (dd, J = 7.8, 4.9Hz, 1H) 7.57 (d, J = 8.8Hz, 2H) 7.76 (d, J = 8.3Hz, 2H) 7.82 (s, 1H) 8.23 (d, J = 7.8Hz, 1H) 8.59 (d, J = 4.4Hz, 1H) 8.74 (d, J = 2.4Hz, 1H) 9.04 - 9.09 (m, 2H) 10.76 (s, 1H) 12.60 (s, 1H).

Example 46: N- {4-r3-fluoro-6- ( ^{'pyridin-3-yl)} -9H-pyrrolor2,3-b: 5,4-c'ldipyridin-4- yllphényl} -amide 61

Step 1: N- (4- {3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] ] dipyridin-4-yl} phenyl) cyclopropanesulfonamide 60

In a reactor, 196 mg of 4- {3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5.4 [α] Dipyridin-4-yl} aniline 57 in 10 ml of tetrahydrofuran and 5 ml of dichloromethane, 0.138 ml of triethylamine and then 55 mg of cyclopropanesulfonyl chloride, seal the tube, subjected to microwave irradiation for 20 minutes at 100 ° ^C. C. The reaction medium is treated with 300 ml of water and then extracted with 3 times 300 ml of ethyl acetate. The combined organic phases are concentrated to dryness under reduced pressure to give 148 mg of N- (4- {3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-4-yl} phenyl) cyclopropanesulfonamide used as a crude in the next step.

Etap_e_2_: N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} cyclopropanesulfonamide 61

In a flask, 148 mg of N- (4- {3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-4-yl} phenyl) cyclopropanesulfonamide 60 in 4.7 ml of tetrahydrofuran and then 30 mg of lithium hydroxide monohydrate dissolved in 0.47 ml of water. The reaction mixture is stirred for 4 h at room temperature and then 30 mg of lithium hydroxide monohydrate are added again. The reaction mixture is stirred for 42 hours at room temperature then concentrated to dryness under reduced pressure. The residue is diluted with 5 ml of DMSO and purified by preparative HPLC, reversed phase in basic medium, eluting with a 10 mM ammonium + water-ammonium formate + ammonia gradient (pH between 9 and 10): acetonitrile to give 37 mg of N - {4- [3-Fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} cyclopropanesulfonamide 61 in powder form beige.

UPLC-MS-DAD-ELSD: Tr (min) = 0.64; [M + H] ⁺ : m / z 460; [MH] ^- : m / z 458. 1H NMR (400MHz, DMSO -? / 6) δ ppm: 1.01 - 1.07 (m, 4H) 2.74 - 2.82 (m, 1H) 7.44 (dd, J = 7.8) , 4.6 Hz, 1H) 7.57 (d, J = 8.8 Hz, 2H) 7.73 (d, J = 8.1 Hz, 2H) 7.78 (d, J = LO Hz, 1H) 8.18 (dt, J = 8.1) , 2.0 Hz, 1H) 8.54 (dd, J = 4.8, 1.6Hz, 1H) 8.73 (d, J = 2.4Hz, 1H) 8.94 (d, J = 17Hz, 1H) 9.06 (d , J = LO Hz, 1H) 10.14 (brs, 1H) 12.55 (brs, 1H).

Example 47: N- {4-rn-fluoro-6- (pyrid-3-yl) -9H-pyrrolor-2,3-b: 5.4-di-dipyridin-4-yl-2-methoxyphenyl} methanesulfonamide 64

Step 1: 4- {3-Fluoro-9 - [(4-methylphenyl) sulfonyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 4-yl} -2-methoxyaniline 62

In a reactor, 250 mg of 3-fluoro-4-iodo-6-pyridin-3-yl-9- (toluene-4-sulphonyl) -9H-pyrrolo [2,3-e] 5,4-c are placed in a reactor. ] dipyridine 18, 343 mg of 4-amino-3-methoxyphenylboronic acid pinacol ester, 53 mg of tetrakis (triphenylphosphine) palladium (0), 224 mg of cesium carbonate in 4 ml of 1,4-dioxane and 1 ml of water, sealed the tube and subjected to microwave irradiation at 125 ⁰ C for 1 h. After 18 hours at room temperature, 300 ml of water are added to the reaction medium and this is then extracted twice with 300 ml of ethyl acetate. The combined organic phases are concentrated to dryness under reduced pressure. The residue is purified by chromatography on a silica column, eluting with a dichloromethane: methanol 100: 0 to 98: 2 mixture to give 113 mg of 4- {3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6- (Pyridin-3-yl) -9Η-pyrrolo [2,3-b: 5,4-c '] dipyridin-4-yl} -2-methoxyaniline 62.

UPLC-MS-DAD-ELSD (LS): Tr (min) = 1.28; (M + H) (+): 540 (+).

Step 2: N- (4- {3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] ] dipyridin-4-yl} -2-methoxyphenyl) methanesulfonamide 63

In a reactor, 113 mg of 4- {3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5.4 [α] Dipyridin-4-yl} -2-methoxyaniline 62 in 10 ml of tetrahydrofuran and 5 ml of dichloromethane, 0.456 ml of triethylamine and then 55 mg of methanesulfonyl chloride, seal the tube and subjected to microwave irradiation 20 min. at 100 ^° C. 300 ml of water are added to the reaction medium and this is then extracted twice with 300 ml of ethyl acetate. The combined organic phases are concentrated to dryness under reduced pressure to give 210 mg of N- (4- {3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-4-yl} -2-methoxyphenyl) methanesulfonamide 63.

UPLC-MS-DAD-ELSD (LS): Tr (min) = 1.27; (M + H) (+): 618 (+); (M-H) (-): 616 (-).

Step 3: N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] -2-methoxyphenyl } methanesulfonamide 64

In a flask, 129 mg of N- (4- {3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-4-yl} -2-methoxyphenyl) methanesulfonamide 63 in 4 ml of tetrahydrofuran and then 26 mg of lithium hydroxide monohydrate dissolved in 0.67 ml of water. The reaction mixture is stirred for 16 hours at room temperature and then 300 ml of water are added and this is then extracted twice with 300 ml of ethyl acetate. The combined organic phases are concentrated to dryness under reduced pressure and the residue is then diluted with 5 ml of DMSO and purified by preparative HPLC, the reverse phase in a basic medium, eluting with a 10 mM ammonium + water + ammonium formate gradient (pH inclusive). between 9 and 10): acetonitrile to give 61 mg of N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine). 4-yl] -2-methoxyphenyl} methanesulfonamide 64 as yellow lyophilisate.

UPLC-MS-DAD-ELSD: Tr (min) = 0.59; [M + H] ⁺ : m / z 464; [MH] -: m / z 462. 1H NMR (400 MHz, DMSO -? / 6)? Ppm: 3.11 (s, 3H) 3.85 (s, 3H) 7.32 (d, J = 8.1 Hz, 1H) ) 7.42 - 7.47 (m, 2H) 7.62 (d, J = 8.1 Hz, 1H) 7.76 (d, J = 0.7Hz, 1H) 8.12 (dt, J = 8.1, 1.7Hz, 1H) 8.54 ( dd, J = 4.6, 1.5 Hz, 1H) 8.74 (d, J = 2.4Hz, 1H) 9.00 (d, J = 17Hz, 1H) 9.07 (d, J = 0.7Hz, 1H) 9.36 (br.s., 1H) 12.58 (br.s., 1H).

Example 48: N- {4- (3-Fluoro-6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-di-dipyridin-4-yl] phenyl} -N-methylmethanesulfonamide 66

Step 1: N-methyl-N- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] methanesulfonamide

In a reactor, 600 mg of 4-methanesulfonylaminophenylboronic acid, pinacol ester, 1.32 g of cesium carbonate in 40 ml of dimethylformamide and then 0.25 ml of iodomethane are placed in the reactor. tube and subjected to microwave irradiation for 20 min at 90 ^° C. The reaction mixture is poured into 2 1 of water and 500 ml of ethyl acetate. After decantation, the organic phase is concentrated in vacuo to give 513 mg of N-methyl-N- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] methanesulfonamide. 65 as a beige oil.

UPLC-MS-DAD-ELSD (LS): Tr (min) = 1.24; (M + H) (+): 312 (+).

Etap_e_2: N- {4- [3-fluoro-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} -N- methylmethanesulfonamide 66

In a reactor, 500 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 19, 518 mg of N-methyl-N- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -phenyl] -methanesulfonamide dissolved in 10 ml of 1,4-dioxane, 407 mg of cesium carbonate, 101 mg of tetrakis (triphenylphosphine) palladium (0) in 7 ml of 1,4-dioxane and 2 ml of water, sealed the tube and subjected to microwave irradiation for 1 hour at 125 ^° C. After 18 h at room temperature are added to the reaction mixture, 1 1 of water and 1 liter of ethyl acetate and the whole is stirred for 30 min at room temperature. The precipitate formed is drained under vacuum and then washed with 50 ml of water and 50 ml of ethyl acetate and dried again under vacuum to give 334 mg of N- {4- [3-fluoro-6- (pyridine) 3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-4-yl] phenyl} -N-methylmethanesulfonamide 66.

UPLC-MS-DAD-ELSD: Tr (min) = 0.64; [M + H] ⁺ : m / z 448; [MH] ^- : m / z 446. 1H NMR (400MHz, DMSO -? / 6) δ ppm: 3.10 (s, 3H) 3.41 (s, 3H) 7.44 (dd, J = 1H, 4.9Hz, m.p. 1H) 7.64 (s, 1H) 7.74 - 7.83 (m, 4H) 8.10 (d, J = 7.8Hz, 1H) 8.54 (d, J = 3.4Hz, 1H) 8.76 (s, 1H) 9.02 (s, 1H) 9.07 (s, 1H) 12.57 (brs, 1H).

Example 49: N- [3- (dimethylamino) propyl] -N- {4-fluoro-6- (pyridin-3-yl) -9H-pyrrolor] 2,3-b: 5,4-dipyridin-4- yllphenyl} methanesulfonamide 68

Step 1: N- [3- (dimethylamino) propyl] -N- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] methanesulfonamide 67

300 mg of 4-methanesulfonylaminophenylboronic acid, pinacol ester, 1.15 g of cesium carbonate in 18 ml of dimethylformamide and then 160 mg of 3-dimethylaminopropyl chloride hydrochloride are introduced into a microwave reactor of suitable size. The tube is sealed and subjected to microwave irradiation for 20 min at 90 ^° C. and then for 1 h at 60 ^° C. The reaction mixture is poured into 500 ml of water and extracted with 300 ml of ethyl acetate. The organic phase is concentrated in vacuo to give 481 mg of N- [3- (dimethylamino) propyl] -N- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) ) phenyl] methanesulfonamide 67 as a colorless oil. UPLC-MS-DAD-ELSD (LS): Tr (min) = 0.69; (M + H) (+): 383 (+). 2nd step :

In a microwave reactor of suitable size are introduced 100 mg of 3-fluoro-4-iodo-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridine 19,294 mg of N- [3- (dimethylamino) propyl] -N- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] methanesulfonamide 67 prepared in step 1, 125 mg of cesium carbonate, 30 mg of tetrakis (triphenylphosphine) palladium (O), 3.6 ml of 1,4-dioxane and 0.6 ml of water. The tube is sealed and subjected to microwave irradiation for 1 h at 125 ^° C. The reaction mixture is poured into 200 ml of water and extracted with 3 times 200 ml of ethyl acetate. The combined organic phases are concentrated in vacuo to give a brown solid. This product is purified by chromatography on a column of silce, eluting with a mixture of dichloromethane: methanol: conc. Ammonia, 100: 0: 0 to 95: 4.5: 0.5 to give 16 mg of N- [3- (dimethylamino) propyl] -N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] phenyl} methanesulfonamide 68 in the form of a yellow solid.

1H NMR (400 MHz, DMSO -? / 6) δ ppm 1.55 to 1.67 (m, 2H); 2.04 (s, 6H); 2.27 (t, J = 6.9 Hz, 2H);

3.12 (s, 3H); 3.82 (t, J = 6.9 Hz, 2H); 7.42 (ddd, J = 0.8 and 4.9 and 8.1 Hz, 1H); 7.62 (d, J = 1.0 Hz, 1

H); 7.76 (d, J = 8.3 Hz, 2H); 7.82 (d, J = 8.3 Hz, 2H); 8.07 (ddd, J = 1, and 2.2 and 8.1 Hz, 1H); 8.54

(dd, J = 1, and 4.9 Hz, 1H); 8.77 (d, J = 2.2 Hz, 1H); 9.01 (dd, J = 0.8 and 2.2 Hz, 1H); 9.07 (d, J = 1.0 Hz,

1H); 12.36 to 12.83 (spread m, 1H).

LC-MS (7 min): Tr (min) = 2.27; [M + H] ⁺ : m / z 519; [M + 2H] ²⁺ : m / z 260 (base peak); [MH] -: m / z 517.

Example 50: 4-R3-Fluoro-6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-di-dipyridin-4-yl-N- (prop-2-en-1) yPaniline 70

Step 1: N- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] prop-2-ene-1-sulfonamide

To 438 mg of 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) aniline in 10 ml of pyridine at 25 ^° C. are added 309 mg of prop-2-chloride. ene-l-sulfonyl. The reaction medium is stirred for 1 h at 25 ^° C. and then concentrated. The residue is taken up in ethyl acetate, the organic phase washed twice with water, dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure to give 625 mg of N- [4- (4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] prop-2-ene-1-sulfonamide 69 as a beige solid.

In a microwave reactor of suitable size, 100 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] were added. ] dipyridine 19 and 207 mg of N-methyl-N- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -phenyl] -methanesulfonamide 69 in 1.0 ml of 1,4-dioxane, then 0.34 ml of aqueous 1.5 M solution of cesium carbonate and 30 mg of tetrakis (triphenylphosphine) palladium (0) are added and subjected to microwave irradiation for 1 hour at 150 ^° C. The suspension is filtered and the filtrate concentrated. The residue is purified by chromatography on a column of silce, eluting with a 0-10% dichloromethane: isopropanol gradient to give 15 mg of 4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2, 3 -b: 5,4-c '] dipyridin-4-yl] -N- (prop-2-en-1-yl) aniline 70 as a yellow solid.

1H NMR (400 MHz, DMSO -? / 6) δ ppm 3.81 to 3.87 (m, 2H); 5.22 (qd, 7 = 1.7 and 10.3 Hz, 1H); 5.33 (qd, J = 1.7 and 17.5Hz, 1H), 5.90 to 6.07 (m, 1H), 6.48 (t, .7 = 6.1Hz, 1H). H); 6.87 (d, / = 8.8 Hz, 2H); 7.44 to 7.55 (m, 3H); 8.02 (d, J = 1.0 Hz, 1H); 8.20 (dt, λ = 2.2 and 8.1 Hz, 1H); 8.56 (dd, J = I, 7 and 4.8 Hz, 1H); 8.63 (d, J = 2.9 Hz, 1H); 9.00 (d, J = 2.2 Hz, 1H); 9.03 (d, J = I ₅ O Hz, 1 H); 12.23 to 12.58 (spread m, 1H). LC-MS (7 min): Tr (min) = 3.44; [M + H] ⁺ : m / z 396; m / z 356 (base peak); [MH] ^": m / z 394.

Examples 51 to 74 (71a-7Ix):

GENERAL PROCEDURE

In a reactor, 0.2 mmol of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine is added. 4 mmol of boronic derivative (acid or ester) in 2 ml of 1,4-dioxane, 0.4 mmol of cesium carbonate in 0.5 ml of water and then under argon 0.02 mmol of tetrakis (triphenylphosphine) palladium (0) in 0.5 ml of dimethylformamide, sealed the tube and stirred at 110 ⁰ C for 18 h. After cooling, the reaction mixture is diluted with 6 ml of 1,4-dioxane, 2 ml of methanol and 0.1 ml of trifluoroacetic acid and then treated for 4 hours at ambient temperature with 150 mg of propanethiol-type resin grafted onto silica. . The reaction mixture is filtered and then washed twice with a 1,4-dioxane: methanol 4: 1 mixture. After evaporation under reduced pressure, the residue is dissolved in 2 ml of dimethylformamide and 0.1 ml of trifluoroacetic acid, filtered and then purified by preparative HPLC, eluting with a gradient of water + 0.1% of trifluoroacetic acid / acetonitrile + 0 , 1% trifluoroacetic acid, 90/10 to 5/95. The products 71a to 71x are detailed in Table 6.

Table 6

Examples 75 to 89 (72a-72o):

GENERAL PROCEDURE FOR THE ARYL AMINATION REACTION (HARTWIG-BUCHWALD)

In a tube, 19 mg of R - (+) - 2,2'-bis (diphenylphosphino) -1,1'-binaphthyl and 6.0 mg of tris (dibenzylideneacetone) dipalladium (0) are placed in 1.25 ml. anhydrous 1,4-dioxane under an argon atmosphere.

In a microwave reactor, 100 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) are placed under argon.

9H-pyrrolo [2,3-b: 5,4-c '] dipyridine 19, 65 mg of potassium tert-butoxide, 5 equivalents of amine, all in 1.25 ml of anhydrous 1,4-dioxane, and then the solution is added. prepared previously, sealed the reactor and subjected to microwave irradiation for 1 h at 140 ^° C.

The reaction mixture is poured onto a mixture of 150 ml of ethyl acetate, 75 ml of water and 75 ml of saturated aqueous sodium bicarbonate solution. After decantation, the organic phase is dried over magnesium sulfate, filtered and evaporated under reduced pressure. The residue is purified by chromatography on a silica column, eluting with a dichloromethane: methanol mixture, 100: 0 to

80: 20 depending on the substrates.

The products are detailed in Table 7 (yield between 31 and 75% depending on the reagents).

Table 7

Example 90: 4-R3-Fluoro-6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-di-dipyridin-4-yl-2-methylbut-3-yn-2-amine 73

In a reactor, 158 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 19, 50 mg of 1,1-dimethyl-prop-2-ynylamine, 23 mg of tetrakis (triphenylphosphine) palladium (0), 3.86 mg of copper iodide (I) in 10 ml of triethylamine, seals the tube and subjected to micro irradiation 1 hour at 120 ^° C. After 18 h at room temperature, the reaction mixture is concentrated under reduced pressure and then dissolved in a mixture of dichloromethane: methanol 50:50 and added with 5 g of silica. After concentration under reduced pressure, the solid deposit is purified by chromatography on a silica column, eluting with a dichloromethane: methanol mixture 100: 0 to 90:10 to give 28 mg of 4- [3-fluoro-6- (pyridin-3 -yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-4-yl] -2-methylbut-3-yn-2-amine 73 as a beige powder.

UPLC-MS-DAD-ELSD: Tr (min) = 2.10; [M + H] ⁺ : m / z 346; [MH] -: m / z 344. 1H NMR (400MHz, DMSO -? / 6)? Ppm: 1.59 (s, 6H) 7.53 (dd, J = 7.9, 4.8Hz, 1H) 8.48 (dt, J = 8.1, 2.0 Hz, 1H) 8.60 (dd, J = 4.6, 1.5 Hz, 1H) 8.70 (d, J = 2.4 Hz, 1H) 8.83 (d, J = 1.0Hz, 1H) 9.10 ( d, J = LO Hz, 1H) 9.31 (d, J = 1.7 Hz, 1H) 12.56 (brs, 1H).

Example 91: 4-R3-Fluoro-6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridin-4-yl] -2-methylbut-3-yl-2-ol 74

In a similar manner to compound 73, 38 mg of 4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] 2-methylbut-3-yn-2-ol are obtained from 158 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5 , 4-c '] dipyridine 19 and 51 mg of 2-methyl-3-butyn-2-ol.

UPLC-MS-DAD-ELSD: Tr (min) = 2.80; [M + H] ⁺ : m / z 347; [MH] -: m / z 345. 1H NMR (400MHz, DMSO -? / 6) δ ppm: 1.68 (s, 6H) 6.05 (s, 1H) 7.54 (dd, J = 8.0, 4.6Hz, m.p. 1H) 8.48 (d, J = 8.0 Hz, 1H) 8.62 (brs, 1H) 8.72 (d, J = 2.4Hz, 1H) 8.87 (d, J = 1.0Hz, 1H) 9.11 (d, J = 1.2Hz, 1H) 9.34 (brs, 1H) 12.59 (s, 1H).

Example 92: 4-R3- (4-ethylpiperazin-1-yl) -3-methylbut-1-yn-1-yl-3-fluoro-6- (pyridin-3-yl) -9H-pyrrolor2,3-b : 5.4-C'ldipyridine 75

Analogously to compound 73, 29 mg of 4- [3- (4-ethylpiperazin-1-yl) -3-methylbut-1-yn-1-yl] -3-fluoro-6- (pyridin-3-yl) ) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridine 75 are obtained from 158 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridine 19 and 109 mg of 1- (1,1-dimethyl-2-propynyl) -4-ethylpiperazine.

UPLC-MS-DAD-ELSD: Tr (min) = 2.42; [M + H] ⁺ : m / z 443; [MH] ^- : m / z 441. 1H NMR (400MHz, DMSO -? / 6) δ ppm: 0.90 (t, J = 7.2Hz, 3H) 1.62 (s, 6H) 2.25 (q, J = 7.2 Hz, 2 H) 2.41 (bursts, 4 H) 2.77 (bursts, 4 H) 7.55 (dd, J = 7.8, 4.9 Hz, 1 H) 8.39 (dt, J = 8.1, 1.8 Hz , 1H) 8.61 (dd, J = 4.8, 11Hz, 1H) 8.71 (d, J = 2.2Hz, 1H) 8.73 (d, J = 0.7 Hz, 1H) 9.12 (d, J = 0.7 Hz , 1H) 9.23 (d, J = 1.5 Hz, 1H) 12.60 (brs, 1H).

Example 93: N, N-Diethyl-2 - ({4-fluoro-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b] -5,4-di-dipyridin-4-yl-2-methylbut-3 -vn-2-yl} oxy) ethanamine 77

Step 1: N, N-diethyl-2 - [(2-methylbut-3-yn-2-yl) oxy] ethanamine 76

1.42 g of 2-methyl-3-butyl-2-ol, 2.91 g of 2-chlorotriethylamine hydrochloride, 4.75 g of potassium hydroxide and 17 ml of potassium hydroxide are introduced into a microwave reactor of suitable size. tetrahydrofuran. The mixture is stirred for 5 min at 25 ^° C. then irradiated for 30 min at 120 ^° C. The medium is diluted with ethyl acetate, washed with water and then treated with a 1N aqueous hydrochloric acid solution. The aqueous phase is alkalinized by addition of aqueous sodium hydroxide and then extracted with ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and concentrated; the product is taken up in ethyl ether, the suspension is filtered and the filtrate is concentrated to give 525 mg of N, N-diethyl-2 - [(2-methylbut-3-yn-2-yl) oxy] ethanamine 76 in the form a yellow liquid. UPLC-SQD: Tr (min) = 0.30; [M + H] ⁺ : m / z 184. Step 2:

In a microwave reactor of suitable size are introduced 103 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridine 19.35 mg of N, N-diethyl-2 - [(2-methylbut-3-yn-2-yl) oxy] ethanamine 76 prepared in step 1, 16 mg of tetrakis (triphenylphosphine) palladium (O) , 3 mg of copper iodide, 1.5 ml of triethylamine and 0.5 ml of DMF. The mixture is irradiated for 1 h at 120 ^° C. 3 mg of copper iodide, 10 mg of tetrakis (triphenylphosphine) palladium (O), 35 mg of the same alkyne as above and 0.5 ml of DMF are added and irradiated. again for 1 h at 120 ^° C. The suspension obtained is diluted with ethyl acetate and with water and then filtered. The organic phase is washed twice with water and then dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue is purified by chromatography on a silica column, eluting with a dichloromethane: methanol mixture, 90:10 to 80:20 to give 44 mg of N, N-diethyl-2 - ({4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-4-yl] -2-methylbut-3-yn-2-yl} oxy) ethanamine 77 in the form of a yellow solid.

IH NMR (400 MHz, DMSO -? / 6) δ ppm 0.63 to 1.33 (m spread, 6H); 1.75 (s, 6H); 2.18 to 3.44 (m partially masked, 6H); 3.71 to 3.99 (m spread, 2 hours); 7.55 (dd, J = 4.9 and 8.0 Hz, 1H); 8.41 (dt, J = 1.8 and 8.0 Hz, 1H); 8.59 to 8.65 (m wide, 1H); 8.68 (bs, 1H); 8.76 (d, J = 2.4 Hz, 1H); 9.13 (d, J = 1.0 Hz, 1H); 9.20 to 9.28 (m wide, 1H); 12.67 (broad, 1H).

LC-MS (7 min): Tr (min) = 2.67; [M + H]: m / z 446; [M + 2H] 2+: m / z 223.5 (base peak); [M-HY m / z 444.

Example 94: 3- {4-Fluoro-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b] -5,4-di-dipyridin-4-yl] phenoxy} -N, N-dimethylpropan-1-amine

In a microwave reactor of suitable size are introduced 75 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c ']. dipyridine 19, 176 mg of boronate, 22 mg of tetrakis (triphenylphosphine) palladium (0), 125 mg, 1.25 ml of dioxane and 02.5 ml of 1.5 M aqueous cesium carbonate solution. The mixture is irradiated for 45 min at 150 ^° C. The suspension obtained is diluted with ethyl acetate and washed three times with water. The organic phase is dried over magnesium sulphate, filtered and then concentrated under reduced pressure. The residue is purified by chromatography on a silica column eluting with a dichloromethane: methanol mixture, 90:10 to 80:20 to give 39 mg of 3- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [ 2,3-b: 5,4-c '] dipyridin-4-yl] phenoxy-N, N-dimethylpropan-1-amine 78 as a yellow solid.

1H NMR (400 MHz, DMSO -? / 6) δ ppm 1.90 to 1.98 (m, 2H); 2.18 (s, 6H); 2.42 (t, J = 6.6 Hz, 2H); 4.17 (t, J = 6.6 Hz, 2H); 7.27 (d, J = 8.3 Hz, 2H); 7.48 (ddd, J = 0.8 and 4.8 and 8.1 Hz, 1H); 7.70 (d, J = 8.3 Hz, 2H); 7.84 (d, J = 1.0 Hz, 1H); 8.17 (ddd, J = 1.7 and 2.2 and 8.1 Hz, 1H); 8.55 (dd, J = 1.7 and 4.8 Hz, 1H); 8.70 (d, J = 2.7 Hz, 1H); 8.97 (dd, J = 0.8 and 2.2 Hz, 1H); 9.06 (d, J = 1.0 Hz, 1H); 12.21 to 12.69 (m spread, 1H).

LC-MS (7 min): Tr (min) = 2.41; [M + H] ⁺ : m / z 442; [M + 2H] ²⁺ : m / z 221.5 (base peak); [MH] -: m / z 440.

Example 95: 4-R3-Fluoro-6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridin-4-ylphenol 79

Analogously to compound 78, from 200 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 19 and 339 mg of 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenol give 32 mg of 4- [3-fluoro-6- (pyridin-3- yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-4-yl] phenol 79 as a yellow solid.

1H NMR (400 MHz, DMSO -? / 6)? Ppm 7.10 (d, J = 8.3 Hz, 2H); 7.49 (ddd, J = 0.8 and 4.8 and 8.1 Hz, 1

H); 7.60 (d, J = 8.3 Hz, 2H); 7.89 (d, J = 1.0 Hz, 1H); 8.19 (ddd, J = 1.7 and 2.2 and 8.1 Hz, 1H); 8.55 (dd, J = I, 7 and 4.8 Hz, 1H); 8.68 (d, J = 2.7 Hz, 1H); 8.97 (dd, J = 0.8 and 2.2 Hz, 1H); 9.06 (d, J = 1.0 Hz, 1H); 9.91 to 10.10 (m spread, 1H); 12.03 to 12.72 (spread m, 1H). LC-MS (7 min): Tr (min) = 2.74; [M + H] ⁺ : m / z 357; [MH] ^- : m / z 355.

Example 96: 2- {4-R3-Fluoro-6- ( ^' pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-c'ldipyridin-4-yl] phenoxy] -N, N-dimethylethanamine 81

Step 1: N, N-dimethyl-2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] ethanamine

In a microwave reactor of suitable size, 220 mg of 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenol, 164 mg of 2-chlorohydrochloride are introduced. dimethylaminoethyl, 1.3 g of cesium carbonate and 4 ml of tetrahydrofuran. The mixture is irradiated for 1 hour at 130 ^° C. The medium is diluted with ethyl acetate and washed 3 times with water. The organic phase is dried over magnesium sulphate, treated with carbon black, filtered and then concentrated under reduced pressure to give 244 mg of N, N-dimethyl-2- [4- (4,4,5,5-tetramethyl) -1 , 3,2-dioxaborolan-2-yl) phenoxy] ethanamine 80 as a brown oil and used crude in the next step.

In a similar manner to compound 78, from 75 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 19 and 176 mg of N, N-dimethyl-2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] ethanamine prepared in step 1, are obtained. 43 mg of 2- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenoxy} -N N, N-dimethylethanamine 81 as a brown solid.

1H NMR (400MHz, DMSO -? / 6) δ ppm 2.42 (s, 6H); 2.84 to 2.98 (m, 2H); 4.29 (t, J = 5.6 Hz, 2H);

7.31 (d, J = 8.6 Hz, 2H); 7.48 (dd, J = 4.8 and 8.1 Hz, 1H); 7.72 (d, J = 8.6 Hz, 2H); 7.84 (d, J = 1.0 Hz,

1H); 8.18 (dt, J = 2.0 and 8.1 Hz, 1H); 8.55 (dd, J = 2.0 and 4.8 Hz, 1H); 8.71 (d, J = 2.7 Hz, 1H); 8.96

(d, J = 2.0 Hz, 1H); 9.07 (d, J = 1.0 Hz, 1H); 12.54 (s, 1H).

UPLC-SQD: Tr (min) = 0.42; [M + H] ⁺ : m / z 428; [M + 2H] ²⁺ : m / z 214.5 (base peak); [MH] ^" : m / z

426.

Example 97: 3-Fluoro-6- (pyrid-3-yl) -4- {4- (2- (pyrrolidin-1-yl) ethoxylphenyl} -9H-pyrrolor2,3-b: 5,4-dipyridine 83

Step 1: 1- {2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] ethyl} pyrrolidine 82

In a similar manner to compound 80, from 220 mg of 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenol and 244 mg of 2-pyrrolidinoethyl bromide hydrochloride 239 mg of 1- {2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] ethyl} pyrrolidine 82 are obtained in the form of an ocher oil. and used raw in the next step.

2nd step :

In a similar manner to compound 78, from 75 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 19 and 183 mg of 1- {2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] ethyl} pyrrolidine prepared in step 1, 32 mg of 3-fluoro-6- (pyridin-3-yl) -4- {4- [2- (pyrrolidin-1-yl) ethoxy] phenyl} -9H-pyrrolo [2,3-b: 5.4. c '] dipyridine 83 as a yellow solid.

1H NMR (400 MHz, DMSO -? / 6) δ ppm 1.83 to 1.88 (broad m, 4H); 2.76 to 3.59 (m partially masked, 6H); 4.33 - 4.39 (wide m, 2H); 7.33 (d, J = 8.5 Hz, 2H); 7.48 (dd, J = 4.7 and 8.1 Hz, 1H); 7.74 (d, J = 8.5 Hz, 2H); 7.84 (s, 1H); 8.20 (dt, J = 1.7 and 8.1 Hz, 1H); 8.55 (dd, J = 1.7 and 4.7 Hz, 1H); 8.72 (d, J = 2.6 Hz, 1H); 8.95 (d, J = U Hz, 1H); 9.07 (s, 1H); 12.56 (wide, 1H). UPLC-SQD: Tr (min) = 0.47; [M + H] ⁺ : m / z 454; [MH] ^- : m / z 452.

Example 98: 3- {4- (3-Fluoro-6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridin-4-yl] phenoxy} -N, N, 2-trimethylpropan -1-Amine 85

Step 1: N, N, 2-Trimethyl-3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] propan-1-amine

In a manner analogous to compound 80, starting from 440 mg of 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenol and 344 mg of 3-dimethylamino chloride hydrochloride -2-methylpropyl (microwave irradiation for 1 h at 150 ^° C.), 594 mg of N, N, 2-trimethyl-3- [4- (4,4,5,5-tetramethyl) -1,3 , 2-dioxaborolan-2-yl) phenoxy] propan-1-amine 84 as a colorless oil and used crude in the next step.

In a similar manner to compound 78, from 75 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 19 and 184 mg of N, N, 2-trimethyl-3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] propan-1-amine prepared at room temperature. Stage 1 gives 26 mg of 3- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4- yl] phenoxy} -N, N, 2-trimethylpropan-1-amine 85 as a yellow solid.

1H NMR (400MHz, DMSO -? / 6) δ ppm 1.09 (d, J = 6.5Hz, 3H); 1.99 to 2.92 (m partially masked, 9H); 3.96 to 4.06 (m, 1H); 4.11 (dd, J = 5.6 and 9.5 Hz, 1H); 7.29 (d, J = 8.5 Hz, 2H); 7.48 (dd, J = 4.7 and 8.1 Hz, 1H); 7.72 (d, J = 8.5 Hz, 2H); 7.84 (brs, 1H); 8.19 (dt, J = 1.7 and 8.1 Hz, 1H); 8.55 (dd, J = 1.7 and 4.7 Hz, 1H); 8.71 (d, J = 2.6 Hz, 1H); 8.95 (d, J = 1.7 Hz, 1H); 9.07 (d, J = 1.0 Hz, 1H); 12.54 (s wide, 1H). LC-MS (7 min): Tr (min) = 2.50; [M + H] ⁺ : m / z 456; [M + 2H] ²⁺ : m / z 228.5 (base peak); [MH] - m / z 454.

Example 99: 3-Fluoro-4- {4- (2- (morphol-4-yl) ethoxylphenyl} -6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridine 87

Step 1: 4- {2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] ethyl} morpholine

In a similar manner to compound 84, from 220 mg of 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenol and 372 mg of 4- (2- chloroethyl) morpholine (microwave irradiation for 1 h at 150 ^° C.), 356 mg of 4- {2- [4- (4,4,5,5-tetramethyl) -1,2,2-dioxaborolan-2 are obtained). (yl) phenoxy] ethyl} morpholine 86 as a white solid and used crude in the next step.

2nd step :

In a similar manner to compound 78, from 75 mg of 3-fluoro-4-iodo-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 19 and 160 mg of 4- {2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] ethyl} morpholine prepared in step 1, 40 mg of 3-fluoro-4- {4- [2- (morpholin-4-yl) ethoxy] phenyl} -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5.4- c '] dipyridine 87 as a yellow solid.

1H NMR (400 MHz, DMSO -? / 6) δ ppm 2.51 to 2.56 (m, 4H); 2.79 (t, J = 5.6 Hz, 2H); 3.58 to 3.64 (m, 4H); 4.27 (t, J = 5.6 Hz, 2H); 7.30 (d, J = 8.4 Hz, 2H); 7.48 (dd, J = 4.7 and 8.1 Hz, 1H); 7.70 (d, J = 8.4 Hz, 2H); 7.83 (d, J = 1.2 Hz, 1H); 8.18 (dt, J = 2.0 and 8.1 Hz, 1H); 8.55 (dd, J = 1.7 and 4.7 Hz, 1H); 8.71 (d, J = 2.7 Hz, 1H); 8.96 (broad d, J = 2.0 Hz, 1H); 9.06 (d, J = 1.2 Hz, 1H); 12.19 to 12.72 (spread m, 1H).

Example 100: N, N-diethyl-2- {4-r3-fluoro-6- ( ^{'pyridin-3-yl)} -9H-pyrrolor2,3-b: 5,4-c'ldipyridin-4- yllphénoxy} ethanamine 89

Step 1: N, N-diethyl-2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] ethanamine 88

440 mg of 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenol, 688 mg of 2-chlorotriethylamine hydrochloride are introduced into a suitable sized microwave reactor. 2.6 g of cesium carbonate and 8 ml of tetrahydrofuran. The mixture is irradiated for 1 h at 150 ^° C. The medium is diluted with ethyl acetate and washed 3 times with water. The organic phase is dried over magnesium sulphate, filtered and then concentrated under reduced pressure to give 640 mg of N, N-diethyl-2- [4- (4,4,5,5-tetramethyl) -1,2,2-dioxaborolan -2-yl) phenoxy] ethanamine 88 as a colorless oil and used crude in the next step.

LC-MS (7 min): Tr (min) = 2.95; [M + H] ⁺ : m / z 320. Step 2:

In a similar manner to compound 78, from 75 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 19 and 184 mg of N, N-diethyl-2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] ethanamine prepared in step 1, are obtained. 20 mg of N, N-diethyl-2- {4- [3-fluoro-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4- yl] phenoxy} ethanol 89 as a beige solid.

1H NMR (400 MHz, DMSO -? / 6) δ ppm 0.80 to 1.53 (m spread, 6H); 2.19-3.71 (m partially masked, 6H); 4.05 to 4.46 (spread m, 2H); 7.31 (broad d, J = 8.5 Hz, 2H); 7.47 (dd, J = 4.8 and 8.1 Hz, 1H); 7.73 (d, J = 8.5 Hz, 2H); 7.84 (s, 1H); 8.19 (broad, J = 8.1 Hz, 1H); 8.55 (d,

J = 4.8 Hz, 1H); 8.71 (d, J = 2.6 Hz, 1H); 8.93 to 8.98 (wide m, 1H); 9.07 (s, 1H); 12.52 (s large, 1

H).

LC-MS (7 min): Tr (min) = 2.43; [M + H] ⁺ : m / z 456; [M + 2H] ²⁺ : m / z 228.5 (base peak); [MH] -: m / z 454.

Example 101: 1- {4-R3-Fluoro-6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-di-dipyridin-4-yl] phenoxy} -3- (morphorm-4- yl) propan-2-ol 90

In a similar manner to compound 78, from 75 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 19 and 210 mg of boronate give 48 mg of 1- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine). 4-yl] phenoxy-3- (morphol-4-yl) propan-2-ol 90. 1H NMR (400 MHz, DMSO -? / 6) δ ppm 2.42 to 2.52 (partially masked m, 6H); 3.55 to 3.60 (m, 4H); 4.02 to 4.11 (m, 2H); 4.13 to 4.20 (m, 1H); 4.94 to 5.00 (m, 1H); 7.30 (d, J = 8.6 Hz, 2H); 7.48 (ddd, J = 0.8 and 4.9 and 8.1 Hz, 1H); 7.71 (d, J = 8.6 Hz, 2H); 7.85 (d, J = 1.0 Hz, 1H); 8.18 (dt, J = 0.9 and 8.1 Hz, 1H); 8.55 (dd, J = 1.7 and 4.9 Hz, 1H); 8.71 (d, J = 2.7 Hz, 1H); 8.97 (broad d, J = 2.0 Hz, 1H); 9.06 (d, J = 1.0 Hz, 1H); 12.43 (s, 1H). UPLC-SQD: Tr (min) = 0.44; [M + H] ⁺ : m / z 500; [MH] -: m / z 498.

Example 102: N-ethyl-3- {4- (3-fluoro-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b] -5,4-di-dipyridin-4-yl] phenoxylpropan-1-amine

Step 1: N-ethyl-3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] propan-1-amine

682 mg of 4- (3-bromopropoxy) benzeneboronic acid pinacolate, 2.0 ml of 2M ethylamine solution in tetrahydrofuran, 2.6 g of sodium carbonate are introduced into a microwave reactor of appropriate size. cesium and 6 ml of tetrahydrofuran. The mixture is irradiated for 1 h at 150 ^° C. The medium is diluted with ethyl acetate and washed 3 times with water. The organic phase is dried over magnesium sulphate, filtered and then concentrated under reduced pressure to give 525 mg of N-ethyl-3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2 -yl) phenoxy] propan-1-amine 91 as a brown oil and used crude in the next step.

UPLC-SQD: Tr (min) = 0.68; [M + H] ⁺ : m / z 306.

Step 2: N-ethyl-3- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenoxy} propan-1-amine 92

Analogously to compound 78, from 125 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 19 and 293 mg of boronate prepared in step 1, give 107 mg of N-ethyl-3- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b] 5,4-c '] dipyrid-4-yl] phenoxy} propan-1-amine 92 as a yellow solid.

1H NMR (400 MHz, DMSO -? / 6) δ ppm 1.16 (t, J = 7.2 Hz, 3H); 2.03 to 2.14 (m, 2H); 2.82 to 2.93 (m, 3H); 3.02 (t, J = 7.2 Hz, 2H); 4.24 (t, J = 6, 1 Hz, 2H); 7.30 (d, J = 8.8 Hz, 2H); 7.49 (dd, J = 4.8 and 8.0 Hz, 1H); 7.73 (d, J = 8.8 Hz, 2H); 7.85 (d, J = 0.5 Hz, 1H); 8.22 (dt, J = 2.0 and 8.0 Hz, 1H); 8.56 (dd, J = 2.0 and 4.8 Hz, 1H); 8.72 (d, J = 2.4 Hz, 1H); 8.95 (d, J = 2.0 Hz, 1H); 9.07 (d, J = 0.5 Hz, 1H). UPLC-SQD: Tr (min) = 0.50; [M + H] ⁺ : m / z 442; [M + 2H] 2 ⁺ : m / z 221.5; [MH] ^- : m / z 440.

Example 103 (94) and Example 104: (2E) -N- [4- (dimethylamino) butyl] -3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b]: 5.4 1-dipyridin-4-hydroxypropan-2-enamide

1 g of 3-fluoro-4-iodo-6-pyridin-3-yl-9- (toluene-4-sulfonyl) -9H-pyrrolo [2,3-e] were introduced into a microwave reactor of suitable size. : 5.4-c] dipyridine 18, 1.24 g of boronate 20, 212 mg of tetrakis (triphenylphosphine) palladium (O), 898 mg of cesium carbonate, 20 ml of dioxane and 5 ml of water. The mixture is irradiated for 1 hour at 120. The reaction medium is poured into a mixture of ethyl acetate and water with vigorous stirring. After separation of the phases, the organic phase is dried over MgSO 4, filtered and then concentrated under reduced pressure. The residue is dissolved in 10 mL of THF and 10 mL of methanol, and then 1.065 g of lithium hydroxide monohydrate dissolved in 5 mL of water is added. After stirring overnight, 100 ml of water are added and the pH is brought to 5 by addition of an aqueous solution of hydrochloric acid. The expected compound is recovered by filtration. 552 mg (80%) of (2E) -3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridm acid are obtained. -4-yl] prop-2-enoic 94.

UPLC-MS-DAD-ELSD (LS): Tr (min) = 0.56; (M + H) (+): 335 (+); (M-H) (-): 333 (-). 2nd step

In a monocolumn, 110 mg of (2E) -3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] acid acid] dipyridin-4-yl] prop-2-enoic 94 are charged together with 10 ml of thionyl chloride. The mixture is heated overnight under reflux with stirring and then concentrated under reduced pressure. The crude product is taken up in 10 ml of dichloromethane, and then 456 μl of 4-dimethylaminobutylam are added. After 1 hour, the reaction medium is concentrated in vacuo. The residue is purified by chromatography on silica gel (25 g of gradient silica dichloromethane / methanol ammonia 2N 100/0 to 90/10), 82 mg (58%) of the expected compound (2E) -N- [4- (dimethylamino) butyl] -3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] prop-2- enamide 95.

1H NMR (400 MHz, DMSO -? / 6) δ ppm: 1.45 to 1.58 (m, 4H); 2.21 (m, 6H); 2.30 at 2.38 (m, 2H);

3.25 to 3.33 (masked m, 2H); 7.15 (d, J = 15.9 Hz, 1H); 7.56 (ddd, J = 1.0 and 4.7 and 8.1 Hz, 1H); 8.14 (d, J = 15.9 Hz, 1H); 8.41 (dt, J = 2.2 and 8.1 Hz, 1H); 8.50 (d, J = I ₅ O ₅ Hz 1H); 8.59 (t, J = 6, ₅ Hz 1H); 8.62 (dd, J = 1.5 and 4.7 Hz, 1H); 8.71 (d, J = 2.9 Hz, 1H); 9.10 (d, J = I ₅ O ₅ Hz 1H); 9.26 (broad d, J = 2.2 Hz, 1H); 12.08 to 13.05 (spread m, 1 H)

UPLC - SQD: Tr (min) = 0.36; [M + H] ⁺ : m / z 433; [MH] ^" : m / z 431 Example 105: 3-Fluoro-4-methoxy-6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-cipyridine 96

In a reactor, 30 mg of 3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 19, 166 mg of sodium methoxide and 37 mg of copper (I) iodide in 0.75 ml of dimethylformamide and 0.45 ml of methanol, seal the tube and irradiate for 1 hour at 60 ^° C. The reaction mixture is poured over 50 ml of ethyl acetate and a mixture of 15 ml of water and 15 ml of saturated aqueous ammonium chloride solution. After decantation, the aqueous phase is extracted with 30 ml of ethyl acetate and the combined organic phases are washed with 40 ml of distilled water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue is purified by chromatography on a silica column, eluting with a 100: 0 to 95: 5 dichloromethane: methanol mixture to give 12 mg of 3-fluoro-4-methoxy-6- (pyridin-3-yl) -9H- pyrrolo [2,3-b: 5,4-c '] dipyridine 96.

UPLC-MS-DAD-ELSD: Tr (min) = 2.48; [M + H] ⁺ : m / z 295; [MH] ^- : m / z 293.

1H NMR (400MHz, DMSO -? / 6)? Ppm: 4.43 (d, J = 5.0Hz, 3H) 7.52 (dd, J = 8.0, 4.7Hz, 1H) 8.49

(d, J = 7.9 Hz, 1H) 8.55 - 8.61 (m, 3H) 9.00 (s, 1H) 9.33 (d, J = 2.2Hz, 1H) 12.31 (brs, 1H).

Example 106: 3- (4-Methylbiperazin-1-yl) -6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridine 97

In a reactor, 28.2 mg of tris (dibenzylideneacetone) dipalladium (0), 36.7 mg of 2-dicyclohexylphosphino2 ', 4', 6'-triisopropylbiphenyl and 86.3 g of potassium tert-butoxide are placed in 6 ml of 1,4-dioxane. After stirring for 5 minutes under argon, 100 mg of 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 6 and 1 ml are added. of 1-methylpiperazine. The reaction mixture is stirred for 5 min at room temperature and then irradiated in the microwave for 1 hour at 140 ^° C. 28.2 mg of tris (dibenzylideneacetone) dipalladium (0), 36.7 mg of 2-dicyclohexylphosphmo-2 ', 4 ', 6'-triisopropylbiphenyl and 86.3 g of potassium tertbutylate are again added and the mixture is irradiated in the microwave Ih at 140 ^° C.

The reaction mixture is concentrated under reduced pressure and then poured into 10 ml of water and 5 ml of ethyl acetate. After decantation, the aqueous phase is extracted with 4 times 5 ml of ethyl acetate and the combined organic phases are washed with an aqueous solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure.

The residue is purified by chromatography on a silica column, eluting with a 100: 0 to 50:50 dichloromethane: isopropanol mixture to give 50 mg of 3- (4-methylpiperazin-1-yl) -6- (pyridin-3-yl). ) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridine 97 as a yellow solid.

UPLC-MS-DAD-ELSD: Tr (min) = 0.82; [M + H] ⁺ : m / z 345; [MH] -: m / z 343. 1H NMR (400MHz, DMSO -? / 6)? Ppm: 2.27 (s, 3H) 2.56 (t, J = 5.1Hz, 4H) 3.22 (t, J = 4.6Hz, 4H) 7.52 (dd, J = I.9, 4.5 Hz, 1H) 8.33 (d, J = 2.9 Hz, 1H) 8.46 - 8.50 (m, 2H) 8.57 (dd, J = 4.8, 1.6Hz, 1H) 8.88 (s) , H) 8.95 (d, J = 1.0 Hz, 1H) 9.34 (d, J = 2.2Hz, 1H) 11.94 (s, 1H).

Example 107 (98) and Example 108: 3- (piperazin-4-yl) -6- (pyridin-3-yl) -9H-pyrrolor2.3-b: 5.4 -idipyridine 99

Step 1: 2-methylpropan-2-methyl-4- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-yl] piperazine-1-carboxylate -yle 98

Analogous to 97, 40 mg of 4- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] piperazine-1-carboxylate 2-methylpropan-2-yl 98 are obtained from 200 mg of 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 6 and 0.468 g of 1-Boc-piperazine. The ligand used for this experiment is 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene.

UPLC-MS-DAD-ELSD: Tr (min) = 3.08; [M + H] ⁺ : m / z 431; [MH] -: m / z 429. 1H NMR (400MHz, DMSO -? / 6) δ ppm: 1.45 (s, 9H) 3.17 (t, J = 4.9Hz, 4H) 3.56 (t, J = 4.6 Hz, 4H) 7.53 (ddd, J = 8.0, 4.7, 0.7Hz, 1H) 8.37 (d, J = 2.7Hz, 1H) 8.46 - 8.51 (m, 2H) 8.58 (dd, J = 4.8) , 1.6 Hz, 1H) 8.87 (s, 1H) 8.97 (d, J = 1.0Hz, 1H) 9.34 (d, J = 2.2Hz, 1H) 12.00 (s, 1H).

Step 2: 3- (piperazin-1-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 99

A mixture of 40 mg of 98 and 4 ml of 4N hydrochloric acid solution in 1,4-dioxane is stirred for 1 hour at room temperature. After concentration, the reaction mixture is diluted with 100 μl of acetic acid and 350 μl of water and then purified by preparative LCMS to give 8.8 mg of 3- (piperazin-1-yl) -6- (pyridin-3- yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine as trifluoroacetic acid salt 99.

UPLC-MS-DAD-ELSD: Tr (min) = 0.28; [M + H] ⁺ : m / z 331.

1H NMR (300 MHz, DMSO -? / 6)? Ppm: 3.40 (masked m, 8H) 7.63 (dd, J = 7.8, 4.9Hz, 1H) 8.41 (d, J = 2.6Hz, 1H) 8.55 (d, J = 2.8Hz, 1H) 8.58 (dd, J = 8.1, 2.0Hz, 1H) 8.64 (dd, J = 4.8, 1.6Hz, 1H) 8.79 (brs, 2H) 8.91 (s, 1H) 9.00 (d, J = 1.1 Hz, 1H) 9.36 (d, J = 2.2Hz, 1H) 12.13 (s, 1H).

Example 109 6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-di-dipyrid-3-amine Step 1: 5'-Chloro-5'-nitro-3,2 ': 4', 3 "-terpyridin-2" -amine 100

4 g of 2-amino-3-bromo-5-nitropyridine, 6.8 g of 5-chloro-4-trimethylstannyl-2- (3'-pyridinyl) -pyridine are placed in a reactor under argon. , 1.49 g of tetrakis (triphenylphosphine) palladium (0) and 734 mg of copper iodide (I) in 80 ml of 1,4-dioxane, sealed the tube. After stirring for 5 minutes under argon, the reactor is subjected to microwave irradiation for 2 hours at 120 ^° C. The reaction medium is concentrated under reduced pressure and then taken up in a 50:50 mixture of dichloromethane: methanol and filtered on clarcel. After concentration under reduced pressure, 7.11 g of 5'-chloro-5 "-nitro-3,2 ': 4', 3" -terpyridin-2 "-amine 100 are obtained in the form of a yellow-brown powder. .

UPLC-MS-DAD-ELSD (LS): Tr (min) = 0.88; (M + H) (+): 328 (+) / ...; (M-H) (-): 326 (-) / ... (presence of a chlorine atom).

Step 2: 5'-Chloro-3,2 ': 4', 3 "-terpyridine-2", 5 "-diamine 101

A mixture of 7.11 g of 5'-chloro-5'-nitro-3,2 ': 4', 3 "-terpyridin-2" -amine 100 and 24.48 g of tin (II) chloride dihydrate in 300 ml of ethanol is refluxed for 2.5 h After concentration under reduced pressure, the reaction mixture is diluted with 1 liter of ethyl acetate and 1 l of water and stirred for 18 h at room temperature. After filtration on Clarcel, the mixture is decanted then the aqueous phase is brought to pH 8 by an aqueous solution of sodium hydrogencarbonate and extracted with 5 times 1 liter of ethyl acetate.The organic phases are combined and then evaporated. under reduced pressure to give 3.67 g of 5'-chloro-3,2 ': 4', 3 "-terpyridine-2", 5 "-diamine 101 as a black powder.

UPLC-MS-DAD-ELSD (LS): Tr (min) = 0.32; (M + H) (+): 298 (+) / ... (presence of a chlorine atom).

Step 3: 6- (Pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-amine

In a tube, 752 mg of (R) - (-) - 1 - [(S) -2-

(dicyclohexylphosphino) ferrocenyl] ethylditerbutylphosphine and 277 mg of palladium (II) acetate in 3 ml of anhydrous 1,4-dioxane under an argon atmosphere and stirred for 10 min at 40 ^° C. In a reactor, 3.97 g of 5'-chloro-3,2 ': 4', 3 "-terpyridine-2", 5 "-diamine 101 and 2.1 g of potassium tert-butoxide are placed in argon under argon. ml of anhydrous 1,4-dioxan and then add the solution prepared previously, seal the tube and subjected to microwave irradiation for 2 h at 125 ^° C. After 18 hours of rest at room temperature, the reaction mixture is poured over 500 ml of water and 500 ml of ethyl acetate, a greenish precipitate appears which is suction-dried under vacuum and is taken up in 50 ml of water acidified with an aqueous solution of 1N hydrochloric acid and then neutralized with water. After filtration and drying under vacuum, the solid obtained is taken up in a mixture of dichloromethane: methanol 50:50, added with 15 g of silica, concentrated under reduced pressure and purified by chromatography on a column of silica eluting with sodium hydroxide. a dichloromethane: methanol mixture 100: 0 to 90:10 to give 911 mg of 6- (p) yridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-3-amine 102 as a yellow powder.

IH NMR (400MHz, DMSO - </ 6) δ ppm 5.10 (s, 2H) 7.50 (dd, J = I.9, 4.8Hz, 1H) 7.81 (d, J = 2.4Hz, 1H) 8.12 (d, J = 2.4Hz, 1H) 8.50 (dt, J = 8.0, 1.9Hz, 1H) 8.56 (dd, J = 4.8, 1.3Hz, 1H) 8.73 (s, 1H) 8.90 (s, 1H) 9.36 (d, J = 2.2Hz, 1H) 11.68 (s, 1H). UPLC-SQD: Tr (min) = 0.24; [M + H] ⁺ : m / z 262.

Example 110: N-propyl-6- (pyrid-3-yl) -9H-pyrrolor-2-b: 5,4-cHdipyridin-3-amine

A mixture of 100 mg of 100 mg of 6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-3-amine 102, 55.8 μl of propionaldehyde and 29 mg of sodium cyanoborohydride in

5 ml of methanol is stirred at room temperature for 18 h. 55.8 μl of propionaldehyde and 29 mg of sodium cyanoborohydride are added and the mixture is stirred for 4 hours at room temperature. To the reaction mixture, 55.8 μl of propionaldehyde and 29 mg of sodium cyanoborohydride are added again and this is then stirred for 18 hours at room temperature. The reaction mixture is diluted with 10 ml of a saturated aqueous solution of sodium hydrogencarbonate and then concentrated under reduced pressure. This is taken up in 200 ml of ethyl acetate and 200 ml of water. After decantation, the organic phase is concentrated under reduced pressure. The residue obtained is taken up in a dichloromethane: methanol 50:50 mixture, supplemented with 2 g of silica, concentrated under reduced pressure to give a solid deposit which is purified by chromatography on a silica column, eluting with a dichloromethane: methanol 100 mixture: 0 to 95: 5 to give 65 mg of N-propyl-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-amine 103 as a a beige powder.

1H NMR (400MHz, DMSO -? / 6)? Ppm: 1.02 (t, J = 7.5Hz, 3H) 1.67 (sxt, J = 7.2Hz, 2H) 3.10 (q, J = 6.8Hz, 2H) 5.66 (t, J = 5.5 Hz, 1H) 7.50 (ddd, J = 8.0, 4.7, 0.7 Hz, 1H) 7.80 (d, J = 2.7 Hz, 1H) 8.17 (d, J = 2.7 Hz, 1H) 8.50 (dt, J = 8.1, 1.7 Hz, 1H) 8.56 (dd, J = 4.6, 1.7 Hz, 1H) 8.81 (d, J = LO Hz, 1H) 8.90 (d, J = I) .2 Hz, 1H) 9.35 (dd, J = 2.2, 0.7 Hz, 1H) 11.70 (brs, 1H). LC-MS (7 min): Tr (min) = 2.28; [M + H] ⁺ : m / z 304.

Example 111: 6- (pyrid-3-yl) -3- (2,2,2-trifluoroethoxy) -9H-pyrrolor2,3-b: 5,4-cidipyridine

In a tube, 5 ml of trifluoroethanol is placed in 0.5 ml of dimethylformamide and 115 mg of 60% sodium hydride in oil is added at 0 ^° C. After stirring at room temperature, this solution is poured into a reactor containing a mixture of 160 mg of 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5.4 [α] dipyridine 6 and 290 mg of copper iodide (I), sealed the tube and subjected to microwave irradiation for 30 min at 140 ^° C. The reaction mixture is diluted with 5 ml of dimethylformamide, filtered through celite then washed with 20 ml of dimethylformamide. After concentration under reduced pressure, the residue is purified by preparative HPLC to give, after lyophilization, 17.5 mg of 6- (pyridin-3-yl) -3- (2,2,2-trifluoroethoxy) -9H-pyrrolo [ 2,3-b: 5,4-c '] dipyridine 104 as a trifluoroacetic acid salt and a light yellow lyophilisate.

1H NMR (400MHz, DMSO -? / 6) δ ppm 4.94 (q, J = 8.8Hz, 2H) 7.74 - 7.80 (m, 1H) 8.54 (s, 2H) 8.68 - 8.77 (m, 2H) ) 8.94 (s, 1H) 9.05 (d, J = LO Hz, 1H) 9.42 (brs, 1H) 12.34 (s, 1H). UPLC-SQD: Tr (min) = 0.59; [M + H] ⁺ : m / z 345; [MH] -: m / z 343.

Example 112: 3-Ethoxy-6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridine

In a flask, 492 mg of 60% sodium hydride in the previously washed oil are placed in 3 times with 2 ml of pentane and 1.3 ml of ethanol. After stirring for 1 hour at room temperature, this solution is poured into a reactor containing 100 mg of 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c]. Dipyridine 6, 146 mg of copper iodide (I) and 0.65 ml of dimethylformamide. The reaction mixture is subjected to microwave irradiation for 1 h at 120 ^° C. and then poured into a mixture of 50 ml of ethyl acetate and an aqueous ammonium chloride solution with vigorous stirring. After decantation, the organic phase is dried over sodium sulfate, filtered and concentrated to dryness. The residue is purified by chromatography on a silica column, eluting with a 100: 0 to 95: 5 dichloromethane: methanol mixture to give 21 mg of 3-ethoxy-6- (pyridin-3-yl) -9H-pyrrolo [2, 3-b: 5.4- [C]] dipyridine 105.

IH NMR (400MHz, DMSO -? / 6) δ ppm 1.43 (t, J = 7.0Hz, 3H) 4.21 (q, J = 1Hz, 2H) 7.53 (dd, J = I.9, 4.8 Hz, 1H) 8.38 (s, 2H) 8.48 (dt, J = 8.1, 2.0Hz, 1H) 8.58 (dd, J = 4.6, 1.5Hz, 1H) 8.88 (s, 1H) 8.98 (d) , J = 0.7Hz, 1H) 9.34 (d, J = 2.0 Hz, 1H) 12.07 (brs, 1H). LC-MS (7 min): Tr (min) = 2.53; [M + H] ⁺ : m / z 291; [MH] ^": m / z 289.

Example 113: 3- (2-Methoxyethoxy) -6- (pyrid-3-yl) -9H-pyrrolo [b]: 5,4-cHdipyridine

In a reactor, 180 mg of 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 6, 169 mg of copper iodide are placed in a reactor. (I), 4.1 ml of 21% sodium methoxyethanoate dissolved in methoxyethanol and 0.4 ml of dimethylformamide, sealed the tube and subjected to microwave irradiation for 45 min at 120 ^° C.

The rest of the protocol is the same as for the compound 105. After purification, 17 mg of 3- (2-methoxyethoxy) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5 are obtained. 4-c '] dipyridine 106.

IH NMR (400MHz, DMSO -? / 6) δ ppm 3.36 (s, 3H) 3.76 (t, J = 4.9Hz, 2H) 4.27 (t, J = 4.4Hz, 2H) 7.53 (dd, J) = 7.9, 4.8 Hz, 1H) 8.39 - 8.41 (m, 2H) 8.48 (dt, J = 8.0, 2.0Hz, 1H) 8.58 (dd, J = 4.6, 1.7Hz, 1H) 8.87 (d, J = 1.0 Hz, 1H) 8.99 (d, J = 1.0Hz, 1H) 9.34 (d, J = 2.2Hz, 1H) 12.11 (brs, 1H). LC-MS (7 min): Tr (min) = 2.31; [M + H] ⁺ : m / z 321; [MH] -: m / z 319.

Example 114: 3-iodo-6- (pyrid-3-yl) -9H-pyrrolor2.3-b: 5.4-cyidipyridine

A mixture of 500 mg of 6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridine 5a in 5 ml of acetic acid and 502 mg of N-iodosuccinimide is stirred at room temperature for 4 h and then heated for 1 h at 80 ^° C. After concentration under reduced pressure, the residue is purified by chromatography on a silica column eluting with a heptane: ethyl acetate 100: 0 to 0: 100 mixture. to give 150 mg of 3-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 107 as a dark brown solid.

1H NMR (400MHz, DMSO -? / 6)? Ppm 7.54 (dd, J = 8.2, 4.8Hz, 1H) 8.48 (dt, J = 1.9, 1.8Hz, 1H)

8.59 (dd, J = 4.6, 1.5 Hz, 1H) 8.77 (d, J = 2.0Hz, 1H) 8.92 (d, J = 0.5Hz, 1H) 9.03 (d, J = LO Hz, 1H) 9.13 (d, J = 2.0Hz, 1H) 9.33 (d, J = 2.4Hz, 1H) 12.38 (brs, 1H).

Examples 115 to 127 (111a-111m)

Step 1: 1-methyl-4- {3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazol-1-yl] propyl} piperazine 108

In a reactor placed under an argon atmosphere, 330 mg of 60% sodium hydride in oil are placed in 1 ml of dimethylformamide and then 500 mg of 4- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -1H-pyrazole dissolved in 4 ml of dimethylformamide dropwise (end of addition temperature close to 32 ° C). At the end of the evolution of gas, 987 mg of 3- (N- methylpiperazine) -propyl bromide dibromhydrate suspended in 20 ml of dimethylformamide. The reaction mixture is stirred for 24 h at room temperature and then poured into a mixture of 100 ml of water and 100 ml of ethyl acetate. After decantation, the aqueous phase is extracted with 4 times 100 ml of ethyl acetate and the combined organic phases are washed once with water, dried over magnesium sulfate, filtered and then concentrated under reduced pressure to give 2 g of 1-methyl-4- {3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazol-1-yl] propyl} piperazine 108 in the form of a colorless oil.

LC (4min) -MS-DAD-ELSD (LS): Tr (min) = 0.76; (M + H) (+): 335 (+).

Etap-2-bis: 2- [3,5-dimethyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazol-1-yl] -N, N- diethylethanamine 109

Analogously to 108, 1.65 g of 2- [3,5-dimethyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazol) 1-yl] -N, N-diethylethanamine 109 as a colorless oil is obtained from 1 g of 3,5-dimethyl-4- (4,4,5,5-tetramethyl-1,3), 2-dioxaborolan-2-yl) -1H-pyrazole and 1.18 g of 2-bromo-N, N-diethylethylamine hydrobromide.

IH NMR (400MHz, DMSO -? / 6) δ ppm 0.89 (t, J = 1Hz, 6H) 1.24 (s, 12H) 2.16 (s, 3H) 2.33 (s, 3H) 2.45 ( q, J = 7.2 Hz, 4H) 2.63 - 2.68 (m, 2H) 3.92 (t, J = 7.0 Hz, 2H).

Step 1b: N, N-diethyl-3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazol-1-yl] propan 1 -amined 110

In a reactor placed under an argon atmosphere, 500 mg of 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazole, 338 mg of 3- diethylamino-1-propanol, 1.91 g of triphenylphosphine supported on resin 1.57 mmol / g in 10 ml of dichloromethane and then added dropwise 0.61 ml of diisopropylazodicarboxylate (end of addition temperature of 32 ° C) . After stirring for 1 hour at room temperature and adding 5 ml of tetrahydrofuran followed by reflux for 6 hours, the reaction mixture is filtered under vacuum, rinsed with tetrahydrofuran and then concentrated under reduced pressure to give 1.42 g of N, N-diethyl-3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazol-1-yl] propan-1-amine 110 in the form of a yellow oil used crude for the rest of the synthesis.

LC (4min) -MS-D AD-ELSD (LS): Tr (min) = 0.95; (M + H) (+): 308 (+). GENERAL PROCEDURE - COUPLING SUZUKI IN POSITION 3

In a reactor, 145 mg of 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridine 6 are placed in 0.5 ml of 1, 2-dimethoxyethane, 1.45 ml of 2 N aqueous sodium carbonate solution, 0.03 equivalents of tetrakis (triphenylphosphine) palladium (0) or 0.15 equivalents of 1,1 '- bis (diphenylphosphino) ferrocenedichloropalladium (II) and 1.6 equivalents boronate (commercial or prepared in step 1), sealed the tube and subjected to microwave irradiation for 10 to 30 min from 120 to 180 ⁰ C. After concentration under reduced pressure, the reaction mixture is purified by chromatography on a silica column, eluting with a 100: 0 to 90: 10 dichloromethane: methanol mixture. The product 111b was also purified by preparative HPLC in an acidic medium using a water + 0.07% trifluoroacetic acid gradient. acetonitrile + 0.07% of trifluoroacetic acid, 95/5 to 40/60. The products 111a to 111m obtained are detailed in Table 8 (yield between 8 and 55% depending on the reagents).

Table 8

Example 128: 3- {1- (1-Ethylpyrrolidin-2-yl) methyl] -1H-pyrazol-4-yl} -6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5.4-c '1dipyridine 113

To 96 mg of 60% sodium hydride in oil in 5 ml of dimethylformamide under argon at 25 ^° C. is added dropwise a solution of 500 mg of 4- (4,4,5,5-tetramethyl) 1,3-dioxaborol-2-yl) -1H-pyrazole in 7 ml of dimethylformamide. After stirring for 30 minutes at 25 ^° C., a solution of 222 mg of N-ethyl-3-chloropiperidine hydrochloride in 7 ml of dimethylformamide is added. The reaction medium is stirred for 2 hours at 25 ^° C. and then for 1 hour at 70 ^° C. and then for 8 hours under reflux. The reaction medium is treated with 20 ml of water and then extracted with 3 times 20 ml of ethyl acetate. The organic phases are combined, washed once with water, dried over magnesium sulfate, filtered and then concentrated under reduced pressure to give 0.8 g of a crude brown oil used in the next reaction (112). In a microwave reactor of suitable size, 524 mg of 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 6 are placed and 786 mg of boronate 112 in 24 ml of 1,2-dimethoxyethane then 6.5 ml of aqueous 2M sodium carbonate solution and 65 mg of tetrakis (triphenylphosphine) palladium (0) are added and subjected to microwave irradiation 10 min at 150 ^° C. 40 mg of tetrakis (triphenylphosphine) palladium (O) are added and irradiated for 5 min at 180 ^° C. The reaction mixture is filtered, rinsed with ethanol and the filtrate concentrated. The crude product is purified by chromatography on a silica column, eluting with a dichloromethane: methanol 100: 0 to 80: 20 mixture and then by preparative HPLC in an acidic medium using a gradient of water + 0.07% of trifluoroacetic acid / acetonitrile + 0 , 07% trifluoroacetic acid, 95: 5 to 20: 80, to give 7 mg of 3- {1 - [(1-ethylpyrrolidin-2-yl) methyl] -1H-pyrazol-4-yl} -6- (Pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 113 as a trifluoroacetic acid salt and a yellow solid.

1H NMR (400 MHz, DMSO -? / 6)? Ppm: 1.22 (t, J = 7.2 Hz, 3H); 1.68 to 2.28 (m, 4H); 3.02 to 3.30 (m, 4H); 3.61 to 3.72 (m, 1H); 4.55 (dd, J = 6.2 and 14.7 Hz, 1H); 4.68 (dd, J = 6.6 and 14.7 Hz, 1H); 7.68 to 7.76 (m, 1H); 8.16 (s, 1H); 8.43 (s, 1H); 8.67 to 8.73 (m, 2H); 8.89 to 8.99 (m, 3H); 9.06 (d, J = 1.0 Hz, 1H); 9.40 (brs, 1H); 9.48 to 9.59 (m spread, 1H); 12.38 (broad, 1H). LC-MS (7 min): Tr (min) = 2.02; [M + H] ⁺ : m / z 424; [MH] ^": m / z 422.

Example 129: 2- (4-R6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c'ldipyridin-3-yl] phenyl} piperazine-1-carboxylate of 2-methylpropan-2- yle 114

In a sealed tube, 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 6 (1.5 g, 4.62 mmol) was placed. ), 4- [4- (4,4,5,5-tetramethyl- [1,2,3] dioxaborolan-2-yl) -phenyl] -piperazine-1-carboxylic acid tert-butyl ester (2.1 g, 6.86 mmol), PdCl ₂ (dppf) (190 mg, 0.233 mmol) and cesium carbonate (3.0 g, 9.21 mmol). The tube is flushed with a stream of nitrogen before adding 1,2-dimethoxyethane (25 ml) and water (2.5 ml). The tube is then sealed and heated at 110 ^° C. for 7 hours. The reaction is then cooled, diluted with water and extracted with a mixture of 10% methylene chloride tetrahydrofuran (60 ml) and saturated aqueous ammonium chloride solution (100 ml). The organic phases are evaporated to dryness and chromatographed on silica with a dichloromethane / methanol mixture. The resulting yellow-brown solid was triturated with cold methanol to give, after drying, a pale yellow solid 114 (1.75 g, 75%).

MS: m / z = 507 (ES +).

1H NMR (300 MHz, DMSO -? / 6)? Ppm: 9.37 (s, 1H), 9.02 (s, 1H), 8.97 (s, 2H), 8.90 (s, 1H), 8.60.

(d, 1H), 8.51 (d, 1H), 7.70 (d, 2H), 7.54 (dd, 1H), 7.13 (d, 2H), 3.50 (t, 4H), 3.28 (t, 4H), 1.44 ( s, 9H).

Example 130: 3- [4- (piperazin-1-yl) phenyl] -6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-c'ldipyridine 115

Compound 114 (600 mg, 1.19 mmol) suspended in methanol (18 ml) with HCl (4 N, 12 ml) is heated at 55 ⁰ C for 5 h. The reaction mixture is cooled to 0 ~ ^40C overnight. The suspension is then filtered and the solid rinsed with a little cold methanol. The orange solid is dried at 50 ^° C. under reduced pressure to give compound 115 in the hydrochloride form (563 mg, 92%).

MS: m / z = 407 (ES +).

1H NMR (300 MHz, DMSO -? / 6) δ ppm 12.73 (s, 1H), 9.53 (s, 1H), 9.24 (s, 3H), 9.11 (s, 1H), 9.08

(d, 1H), 8.99 (d, 2H), 8.87 (d, 1H), 8.08 (dd, 1H), 7.76 (d, 2H), 7.18 (d, 2H), 3.48 (t, 4H), 3.22 ( m, 4H).

Example 131: 2-Methylpropan-2- 2- (3-r6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-c'ldipyridin-3-yllphenyl} piperazine-1-carboxylate yle 116

Compound 116 is prepared in the same manner as compound 114 from 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridine 6 ( 600 mg, 1.85 mmol) and 4- [3- (4,4,5,5-tetramethyl- [1,2,3] dioxaborolan-2-yl) -phenyl] -piperazine-1-carboxylic acid tert -butyl ester (930 mg, 2.39 mmol) to give 116 as a brown solid (824 mg, 80%).

MS: m / z = 507 (ES +).

1H NMR (300 MHz, DMSO -? / 6) δ ppm 12.37 (s, 1H), 9.38 (s, 1H), 9.05 (s, 1H), 9.04 (s, 1H), 8.98 (s, 1H), 8.95; (s, 1H), 8.60 (d, 1H), 8.52 (d, 1H), 7.55 (dd, 1H), 7.40 (t, 1H), 7.37 (s, 1H), 7.26 (d, 1H), 7.02 ( d, 1H), 3.51 (t, 4H), 3.25 (t, 4H), 1.44 (s, 9H).

Example 132: 3- [3- (piperazin-1-yl) phenyl] -6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridine 117

Compound 117 is prepared from 116 (670 mg, 1.32 mmol) as for compound 115 to give a yellow solid as the hydrochloride salt (636 mg, 93%).

MS: m / z = 407 (ES +).

1H NMR (300 MHz, DMSO -? / 6) δ ppm 12.63 (s, 1H), 9.51 (s, 1H), 9.19 (s, 1H), 9.13 (d, 1H), 9.11 (s, 1H), 9.06 (s, 1H), 9.01 (s, 1H), 8.54 (d, 1H), 8.01 (dd, 1H), 7.45 (t, 1H), 7.42 (s, 1H), 7.32 (d, 1H), 7.08 ( d, 1H), 3.52 (t, 4H), 3.27 (m, 4H).

Example 133: N, N-4-Triethyl-5-r6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyrid-3-ylpyrid-2-amine 118

Compound 118 is prepared according to the procedure of compound 114 from 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 6 (120 mg. 0.369 mmol) and 6-diethylamino-4-ethyl-pyrid-3-yl boronic acid (160 mg, 0.721 mmol). After purification by preparative HPLC (acetonitrile / H ₂ O with 0.1% trifluoroacetic acid) are obtained 50 mg of product 118 as a trifluoroacetic acid salt. MS: m / z = 423 (ES +).

1H NMR (300 MHz, DMSO -? / 6)? Ppm: 12.58 (s, 1H), 9.42 (s, 1H), 9.11 (s, 1H), 9.02 (s, 1H), 8.76 (s, 1H), 8.73 (d, 1H), 8.71 (d, 1H), 8.63 (s, 1H), 7.96 (s, 1H), 7.75 (dd, 1H), 7.09 (s, 1H), 3.65 (q, 4H), 2.72. (q, 2H), 1.23 (t, 6H), 1.06 (t, 3H).

Example 134: 2- (Dimethylamino) -1- (4- {3- (6-pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-di-dipyrid-3-yl] phenylpiperazin-1-yl ) ethanone 119

Compound 117 (70 mg, 0.136 mmol) and N, N-dimethylglycyl chloride hydrochloride (49 mg, 0.310 mmol) are placed in a keller. Anhydrous pyridine (1 ml) is added under nitrogen and then N, N-diisopropylethylamine (148 mg, 1.15 mmol). The orange suspension is then stirred for 1.5 h and then diluted with a saturated aqueous solution of sodium bicarbonate and extracted with 10% dichloromethane tetrahydrofuran (30 ml x 5). The combined organic phases are dried over MgSO ₄ and concentrated to dryness. The solid obtained is dried under reduced pressure at 50 ^° C. to give compound 119 in the form of a cream-white solid (56 mg, 84%).

MS: m / z = 492 (ES +).

1H NMR (300 MHz, DMSO -? / 6) δ ppm 12.37 (s, 1H), 9.38 (s, 1H), 9.06 (s, 1H), 9.05 (s, 1H), 8.99 (s, 1H), 8.96; (s, 1H), 8.60 (t, 1H), 8.52 (dt, 1H), 7.55 (dd, 1H), 7.41 (t, 1H), 7.38 (s, 1H), 7.27 (d, 1H), 7.03 ( d, 1H), 3.68 (m, 4H), 3.52 (s, 2H), 3.32 (m, 4H), 2.41 (s, 6H).

Example 135: 2- (Dimethylamino) -1- (4- {4-r6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridin-3-yl] phenylpiperazin-1 -vethanone 120

Compound 120 is prepared as 119 using compound 115 (70 mg, 0.136 mmol) to give a bright white solid (42 mg, 63%).

MS: m / z = 492 (ES +).

1H NMR (300 MHz, DMSO -? / 6)? Ppm 12.30 (s, 1H), 9.37 (s, 1H), 9.03 (s, 2H), 8.99 (s, 1H), 8.90 (s, 1H), 8.60. (d, 1H), 8.51 (dd, 1H), 7.72 (d, 2H), 7.55 (dd, 1H), 7.15 (d, 2H), 3.71 (t, 2H), 3.64 (t, 2H), 3.25 ( m, 4H), 3.22 (s, 2H), 2.25 (s, 6H).

Example 136: 1- (4- (3-R6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-cidipyridin-3-yl] phenyl} piperazin-1-yl) ethanone 121

To a suspension of the compound 117 (70 mg, 0.136 mmol) in dichloromethane (1.5 ml) is added N, N-diisopropylethylamine (74 mg, 0.1 ml, 0.574 mmol). The reaction is stirred at 25 ^° C. for 15 min and then acetyl chloride (22 mg, 0.28 mmol) is added. After stirring at 25 ^° C. for 1 h, acetyl chloride (22 mg) and N, N-diisopropylethylamine (0.2 ml) are added. After another 15 minutes, methanol (0.5 ml) is added and concentrated to dryness. The residue is partitioned between a saturated aqueous solution of sodium bicarbonate and dichloromethane and then the aqueous phase is re-extracted with dichloromethane (30 ml × 5). The organic phases are dried over MgSO ₄ and concentrated to dryness. The residue is stirred with LiOH (5 mg) in methanol (5 ml + a few% water) for 30 min. The solution is evaporated to dryness and the residue obtained is again partitioned between a saturated aqueous solution of sodium bicarbonate and dichloromethane and the aqueous phase is re-extracted with dichloromethane. The organic phases are dried over MgSO ₄ and concentrated to dryness and the solid obtained is dried under reduced pressure at 50 ^° C. to give compound 121 in the form of a red-orange solid (38 mg, 62%).

MS: m / z = 449 (ES +).

1H NMR (300 MHz, DMSO -? / 6) δ ppm 9.38 (s, 1H), 9.04 (s, 2H), 8.97 (s, 1H), 8.94 (s, 1H), 8.59 (d, 1H), 8.52 (d, 1H), 7.54 (dd, 1H), 7.40 (t, 1H), 7.37 (s, 1H), 7.26 (d, 1H), 7.02 (d, 1H), 3.60 (m, 4H), 3.26 ( m, 4H), 2.07 (s, 3H).

Example 137: 1- (4- (4-R6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-di-dipyridin-3-yl] phenyl} piperazin-1-deoxyethanone 122

Compound 122 is prepared following the procedure of compound 121 from compound 115 (70 mg, 0.136 mmol). The crude product (26 mg) is purified by SPE chromatography (SCX cartridge eluted with a 7 N ammonia solution / methanol in dichloromethane) and then trituration in methanol to give 9 mg (15%) of product in the form of an orange solid.

MS: m / z = 449 (ES +).

1H NMR (300 MHz, DMSO -? / 6) δ ppm 12.30 (s, 1H), 9.38 (s, 1H), 9.03 (s, 1H), 8.99 (s, 2H), 8.90 (s, 1H), 8.60. (s, 1H), 8.52 (d, 1H), 7.72 (d, 2H), 7.55 (dd, 1H), 7.14 (d, 2H), 3.60 (t, 4H), 3.26 (t, 2H), 3.20 ( t, 2H), 2.07 (s, 3H).

Example 138: 3- [4- (4-methylpiperazin-1-yl) phenyl] -6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-dipyridine 123

Compound 115 (70 mg, 0.136 mmol) and sodium triacetoxyborohydride (370 mg, 1.75 mmol) in 1,2-dichloroethane (4 ml) were stirred at 25 ⁰ C for 20 min, then a aqueous solution of HCHO (0.026 ml, 37%, 0.347 mmol). The mixture is stirred overnight and then diluted with a mixture of saturated aqueous solution of sodium bicarbonate and dichloromethane. The aqueous phases are re-extracted with dichloromethane (30 ml × 12). The combined organic phases are dried on MgSO 4, concentrated and dried at 50 ^° C. under reduced pressure to give compound 123 in the form of a yellow solid (54 mg, 74%).

MS: m / z = 421 (ES +).

1H NMR (300 MHz, DMSO -? / 6)? Ppm 12.32 (br, 1H), 9.38 (s, 1H), 9.03 (s, 1H), 9.02 (s, 1H), 8.97 (d, 1H), 8.89; (s, 1H), 8.60 (t, 1H), 8.52 (t, 1H), 7.70 (d, 2H), 7.55 (dt, 1H), 7.11 (d, 2H), 3.24 (m, 8H), 2.24 ( s, 3H).

Example 139: 3- [3- (4-methylpiperazin-1-yl) phenyl] -6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4 -idipyridine 124

Compound 124 is prepared according to the procedure of compound 123 from compound 117 (70 mg, 0.136 mmol) to give a white solid (49 mg, 86%).

MS: m / z = 421 (ES +).

1H NMR (300 MHz, DMSO -? / 6)? Ppm 12.35 (s, 1H), 9.38 (s, 1H), 9.04 (s, 2H), 9.00 (s, 1H), 8.94 (s, 1H), 8.60. (d, 1H), 8.52 (d, 1H), 7.55 (dd, 1H), 7.35 (t, 1H), 7.33 (s, 1H), 7.21 (d, 1H), 7.00 (d, 1H), 3.28 ( m, 8H), 2.25 (s, 3H).

Example 140: 3- {3- [4- (propan-2-yl) piperazin-1-yl] phenyl} -6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-dipyridine 125

Compound 125 is prepared according to the procedure of compound 123 from compound 115 (70 mg, 0.136 mmol) and acetone (78 mg, 1.35 mmol) to give a white solid (52 mg, 85%).

MS: m / z = 449 (ES +).

1H NMR (300 MHz, DMSO -? / 6)? Ppm 12.36 (s, 1H), 9.38 (s, 1H), 9.04 (s, 2H), 9.00 (s, 1H), 8.94 (s, 1H), 8.60. (d, 1H), 8.52 (d, 1H), 7.55 (dd, 1H), 7.37 (t, 1H), 7.32 (s, 1H), 7.22 (d, 1H), 7.00 (s, 1H), 3.26 ( m, 4H), 2.70 (m, 1H), 2.63 (m, 4H), 1.08 (t, 6H).

Example 141: 3- [4- (4-Cyclopropylpiperazin-1-yl) phenyl] -6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4 -idipyridine 126

To a suspension of compound 115 (100 mg, 0.194 mmol) and milled 4 Å molecular sieve (200 mg) in methanol (5 ml) was added (1-ethoxy-cyclopropoxy) -trimethylsilane (200 mg, 1.15 mmol), acetic acid (115 mg, 1.92 mmol) and sodium cyanoborohydride (1 M solution in tetrahydrofuran, 0.87 ml, 0.87 mmol). After having been heated at 60 ^° C. for 7 h, the reaction is cooled and partitioned between a saturated aqueous solution of sodium bicarbonate and dichloromethane. The aqueous phases are re-extracted with dichloromethane (30ml x 6). The combined organic phases are concentrated to dryness and dried at 50 ^° C. under reduced pressure to give 66 mg of a beige solid. This solid is purified by SPE chromatography (SCX 10% 7N NH ₃ / methanol in dichloromethane). 44 mg of a yellow solid are obtained which are triturated in methanol to give 40 mg of a yellow solid 126 (29%).

MS: m / z = 447 (ES +).

1H NMR (300 MHz, DMSO -? / 6)? Ppm 12.28 (s, 1H), 9.37 (s, 1H), 9.03 (s, 1H), 8.99 (s, 1H), 8.97 (s, 1H), 8.89; (s, 1H), 8.60 (d, 1H), 8.51 (d, 1H), 7.69 (d, 2H), 7.55 (dd, 1H), 7.10 (d, 2H), 3.19 (t, 4H), 2.71 ( t, 4H), 1.68 (m, 1H), 0.45 (m, 2H), 0.37 (m, 2H).

Example 142: 3- [3- (4-Cyclopropylpiperazin-1-yl) phenyl] -6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-dipyridine 127

Compound 127 is prepared according to the procedure of compound 126 from compound 117 (100 mg, 0.194 mmol). The crude product obtained (97 mg) is purified by SPE chromatography (SCX, 10% 7N ammoniacal solution in methanol in dichloromethane) to give 58 mg (42%) of an off-white solid.

MS: m / z = 447 (ES +).

1H NMR (300 MHz, DMSO -? / 6)? Ppm 12.35 (s, 1H), 9.38 (s, 1H), 9.04 (s, 2H), 8.99 (s, 1H), 8.93 (s, 1H), 8.60. (d, 1H), 8.52 (d, 1H), 7.55 (dd, 1H), 7.37 (t, 1H), 7.33 (s, 1H), 7.22 (d, 1H), 6.99 (d, 1H), 3.24 (d, 1H), t, 4H), 2.73 (t, 4H), 1.70 (m, 1H), 0.44 (m, 2H), 0.38 (m, 2H).

Example 143: 4- {4-R6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-c'ldipyrid-3-yllpyrid-2-yl} piperazine-1-carboxylate 2 methylpropan-2-yl 128

Compound 128 is prepared according to the procedure of compound 116 from 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridine 6 (150 mg 0.462 mmol) and 4- [4- (4,4,5,5-tetramethyl- [1,2,3] dioxaborolan-2-yl) -pyridin-2-yl] piperazine-1-carboxylic acid tert- butyl ester (270 mg, 0.694 mmol), to give a white solid (160 mg, 68%).

MS: m / z = 508 (ES +).

1H NMR (300 MHz, DMSO -? / 6) δ ppm 12.50 (s, 1H), 9.38 (s, 1H), 9.18 (s, 1H), 9.07 (s, 2H), 8.97 (s, 1H), 8.61 (d, 1H), 8.52 (d, 1H), 8.26 (d, 1H), 7.55 (dd, 1H), 7.28 (s, 1H), 7.17 (d, 1H), 3.64 (m, 4H), 3.50 ( m, 4H), 1.44 (s, 9H).

Example 144: 3- [2- (piperazin-1-yl) pyrid-4-yl] -6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridine 129

Compound 129 was prepared according to the procedure of compound 117 from compound 128 (108 mg, 0.213 mmol), to give the expected compound (hydrochloride, 4 HCl, 100 mg, 86%) as a yellow solid.

MS: m / z = 408 (ES +).

1H NMR (300 MHz, DMSO -? / 6) δ ppm 12.95 (s, 1H), 9.63 (br, 2H), 9.53 (s, 1H), 9.39 (s, 1H), 9.28 (s, 1H), 9.25. (s, 1H), 9.16 (t, 1H), 9.14 (s, 1H), 8.93 (d, 1H), 8.27 (d, 1H), 8.16 (dd, 1H), 7.72 (s, 1H), 7.46 ( d, 1H), 4.10 (br, 4H), 3.30 (br, 4H).

Example 145: N, N-Dimethyl-3 - ({5- (6-pyrid-3-yl) -9H-pyrrolo [2,3-b] -5,4-di-dipyrid-3-yl] pyridin-2-yl} oxy ) propan-1-amine 130

Compound 130 is prepared according to the procedure of compound 114 from 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 6 (150 mg 0.462 mmol) and dimethyl- {3- [5- (4,4,5,5-tetramethyl- [1,2,3] dioxaborolan-2-yl) -pyridin-2-yloxy] -propyl} -amine (184 mg, 0.60 mmol), to give a beige solid (80 mg, 41%).

MS: m / z = 425 (ES +).

1H NMR (300 MHz, DMSO -? / 6)? Ppm 12.40 (s, 1H), 9.36 (s, 1H), 9.05 (s, 2H), 8.96 (s, 1H), 8.93 (s, 1H), 8.61. (s, 1H), 8.60 (d, 1H), 8.51 (d, 1H), 8.16 (d, 1H), 7.55 (dd, 1H), 6.99 (d, 1H), 4.36 (t, 2H), 2.38 ( t, 2H), 1.99 (s, 6H), 1.90 (m, 2H).

Example 146: N, N-dimethyl-3- {4- (6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yliphenoxylpropan-1-amine 131

A suspension of 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 6 (250 mg, 0.77 mmol), dimethyl- 3- [4- (4,4,5,5-tetramethyl- [1,2,3] dioxaborolan-2-yl) -phenoxy] -propyl} -amine (250 mg, 0.82 mmol), Pd ( PPh ₃ ) ₄ (44 mg, 0.039 mmol) and cesium carbonate (627 mg, 1.9 mmol) in 1,2-dimethoxyethane (2.5 ml) and water (0.25 ml) is heated to 105 ⁰ C under nitrogen in sealed tube for 23 h. The reaction mixture is diluted with dichloromethane / tetrahydrofuran / methanol and filtered through Celite. The filtrate is concentrated to dryness and the residue is chromatographed (silica gel pretreated with 1% triethylamine in dichloromethane and then eluent dichloromethane / methanol) to give the product 131 in the form of a white solid (41 mg, 13%). %).

MS: m / z = 424 (ES +).

1H NMR (300 MHz, DMSO -? / 6) δ ppm 12.32 (s, 1H), 9.37 (s, 1H), 9.03 (s, 1H), 9.00 (s, 1H), 8.99 (s, 1H), 8.90 (s, 1H), (s, 1H), 8.59 (d, 1H), 8.51 (d, 1H), 7.75 (d, 2H), 7.55 (dd, 1H), 7.10 (d, 2H), 4.08 (t, 2H), 2.39 ( t, 2H), 2.17 (s, 6H), 1.89 (t, 2H).

Example 147: 3- {4- (3- (Piperidyl-1-yl) propoxylphenyl} -6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridine 132

Compound 132 is prepared according to the procedure of compound 131 from 1- {3- [4- (4,4,5-tetramethyl- [1,2,3] dioxaborolan-2-yl) -phenoxy] propylpiperidine (397 mg, 1.15 mmol) and 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 6 (250 mg, 0.77 mmol) to give the expected product (92 mg, 26%) as a white solid.

MS: m / z = 464 (ES +).

1H NMR (300 MHz, DMSO -? / 6) δ ppm 12.32 (s, 1H), 9.37 (s, 1H), 9.03 (s, 1H), 9.00 (s, 1H), 8.99 (s, 1H), 8.89; (s, 1H), 8.59 (d, 1H), 8.51 (d, 1H), 7.75 (d, 2H), 7.55 (dd, 1H), 7.10 (d, 2H), 4.08 (t, 2H), 2.42- 2.36 (m, 6H), 1.90 (p, 2H), 1.51 (m, 4H), 1.39 (m, 2H).

Example 148: 3- {4- [2- ( ^' Morpholin-4-yl) ethoxylphenyl] -6- ( ^' pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridine 133

Compound 133 is prepared according to the procedure of compound 131 from 4- {2- [4- (4,4,5,5-tetramethyl- [1,2,3] dioxaborolan-2-yl) -phenoxy] - ethyl-morpholine (383 mg, 1.15 mmol) and 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 6 (250 mg, 0.77 mmol) to give the expected product (45 mg, 13%) as a white solid.

MS: m / z = 452 (ES +).

1H NMR (300 MHz, DMSO -? / 6) δ ppm 12.36 (s, 1H), 9.39 (s, 1H), 9.04 (s, 1H), 9.01 (s, 1H), 8.99 (s, 1H), 8.91; (s, 1H), 8.62 (m, 1H), 8.52 (d, 1H), 7.83 (d, 2H), 7.56 (m, 1H), 7.16 (d, 2H), 4.30 (m, 2H), 3.71 ( m, 4H), 3.20-2.50 (m, 6H).

Example 149: 3- {4-R3- (Morphol-4-yl) propoxylphenyl} -6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4 -idipyridine 134

Compound 134 is prepared according to the procedure of compound 131 from 4- {3- [4- (4,4,5-tetramethyl- [1,2,3] dioxaborolan-2-yl) -phenoxy] -propyl } -morpholine (399 mg, 1.15 mmol) and 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 6 (250 mg) 0.77 mmol) to give the expected product (125 mg, 35%) as a white solid.

MS: m / z = 466 (ES +).

1H NMR (300 MHz, DMSO -? / 6) δ ppm 12.32 (s, 1H), 9.37 (s, 1H), 9.03 (s, 1H), 9.00 (s, 1H), 8.99 (s, 1H), 8.90 (s, 1H), (s, 1H), 8.59 (d, 1H), 8.51 (d, 1H), 7.75 (d, 2H), 7.55 (dd, 1H), 7.11 (d, 2H), 4.09 (t, 2H), 3.60 ( t, 4H), 2.47-2.40 (m, 6H), 1.92 (p, 2H).

Example 150: 3- {4- [2- (1H-Imidazol-1-yl) ethoxylphenyl} -6- (pyridin-3-yl) -9H-pyrrolor] 2,3-b: 5.4-isidyridine 135

Compound 135 is prepared according to the procedure of compound 131 from 1- {2- [4- (4,4,5,5-tetramethyl- [1,2,3] dioxaborolan-2-yl) -phenoxy] - ethyl-1H-imidazole (250 mg, 1.08 mmol) and 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 6 (250 mg, 0.77 mmol), to give the expected product (72 mg, 22%) as a white solid.

MS: m / z = 433 (ES +).

1H NMR (300 MHz, DMSO -? / 6) δ ppm 12.30, 9.37 (s, 1H), 9.03 (s, 1H), 9.00 (s, 1H), 8.98 (s, 1H), 8.89 (s, 1H); 8.59 (d, 1H), 8.51 (d, 1H), 7.76 (d, 2H), 7.55 (dd, 1H), 7.29 (s, 1H), 7.12 (d, 2H), 6.93 (s, 1H), 4.41 (t, 2H), 4.34 (t, 2H).

Example 151: 4-R6- (pyrid-3-yl) -9H-pyrrolor2.3-b: 5.4-cisldipyridin-3-ylphenol 136

Compound 136 is prepared according to the procedure of compound 131 from 4- (4,4,5,5-tetramethyl- [1,2,3] dioxaborolan-2-yl) -phenol (305 mg, 1.39 mmol). ) and 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridine 6 (200 mg, 0.62 mmol), to give the product expected (37 mg, 18%) as a white solid.

MS: m / z = 339 (ES +).

1H NMR (300 MHz, DMSO -? / 6) δ ppm 12.27 (s, 1H), 9.60 (s, 1H), 9.36 (s, 1H), 9.02 (s, 1H), 8.88

(s, 1H), 8.86 (s, 1H), 8.83 (d, 1H), 8.60 (d, 1H), 8.50 (d, 1H), 7.62 (d, 2H), 7.55 (dd, 1H), 6.93 ( d, 2H).

Example 152: 3- (4- {3- (4- (methylsulfonyl) piperazin-1-ylpropoxy} phenyl) -6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridine 138

Step 1: 1- (Methylsulfonyl) -4- {3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] propyl} piperazine 137

A suspension of 2- [4- (3-bromo-propoxy) -phenyl] -4,4,5,5-tetramethyl- [1,2,2] dioxaborolan (350 mg, 1.03 mmol), 1 - (Methylsulfonyl) piperazine (185 mg, 1.13 mmol) and cesium carbonate (336 mg, 1.03 mmol) in tetrahydrofuran (3.0 ml) is heated at 150 ^° C. under a microwave for 1 hour. The reaction is then concentrated to dryness and the residue is washed with water, triturated with toluene and then with ether to give the expected product 137 (520 mg) in the form of a whitish gel.

MS: m / z = 424.2 (ES +).

1H NMR (300 MHz, CDCl ₃ ) δ ppm 7.75 (d, 2H), 7.25 (s, 1H), 6.85 (d, 2H), 4.04 (t, 2H), 3.25 (t,

4H), 2.79 (s, 3H), 3.62-3.50 (m, 6H), 1.94 (p, 2H), 1.32 (s, 12H).

Compound 138 is prepared following the procedure of compound 131 from 137 (used crude, 520 mg, 1.03 mmol) and 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3 -b: 5,4-c '] dipyridine 6 (250 mg, 0.77 mmol) to give the expected product (118 mg, 28%) as a white solid.

MS: m / z = 543 (ES +).

1H NMR (300 MHz, CDCl ₃ + methanol-d ₄ ) δ ppm 9.21 (s, 1H), 9.04 (s, 1H), 8.78 (s, 1H), 8.68 (s, 1H), 8.58 (d, 1H) 8.46 (s, 1H), 8.43 (d, 1H), 7.62 (d, 2H), 7.50 (dd, 1H), 7.06 (d, 2H), 4.12 (t, 2H), 3.29 (m, 4H), 2.83 (s, 3H), 2.65 (m, 6H), 2.05 (t, 2H).

Example 153: N, N-diethyl-2- {3- (6- (pyrid-3-yl) -9H-pyrrolor-2,3-b: 5.4-di-dipyridin-3-yl] phenoxy} ethanamine 140

Step 1: N, N-diethyl-2- [3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] ethanamine 139

139 is prepared according to the procedure of compound 137 from 2- [3- (2-bromoethoxy) -phenyl] -4,4,5,5-tetramethyl- [1,2,3] dioxaborolane (300 mg, 0.92 mmol) and diethylamine (104 mg, 1.43 mmol), to give the expected product 139 (262 mg, 89%) as a yellow oil.

MS: m / z = 320 (ES +).

1H NMR (300 MHz, CDCl ₃ ) δ ppm 7.46-7.26 (m, 3H), 7.03 (s, 1H), 4.10 (t, 2H), 2.89 (t, 2H), 2.64

(q, 4H), 1.35 (s, 12H), 1.10 (t, 6H).

Compound 140 is prepared following the procedure of compound 131 from 139 (used crude, 259 mg, 0.81 mmol) and 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3 -b: 5,4-c '] dipyridine 6 (200 mg, 0.62 mmol), to give the expected product (56 mg, 21%) as a white solid.

MS: m / z = 438 (ES +).

1H NMR (300 MHz, CDCl ₃ + methanol-d ₄ ) δ ppm 9.24 (s, 1H), 9.05 (s, 1H), 8.80 (s, 1H), 8.75 (s, 1H), 8.58 (d, 1H) , 8.40 (d, 1H), 7.42 (d, 1H), 7.33 (d, 1H), 7.32 (s, 1H), 6.97 (dd, 1H), 4.58 (t, 2H), 3.50 (t, 2H), 3.28 (q, 4H), 1.45 (t, 6H).

Example 154 (142) and Example 155: 3- {4-R6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-di-dipyridin-3-yl] phenoxypropan-1-amine 143

Step 1: 2-Methylpropan-2-yl {3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] propyl} carbamate

141 is prepared following the procedure of 137 from 4- (4,4,5,5-tetramethyl- [1,2,3] dioxaborolan-2-yl) -phenol (264 mg, 1.2 mmol) and from 2-methylpropan-2-yl (3-bromopropyl) carbamate (450 mg, 1.89 mmol) to give a brown oil (500 mg).

MS: m / z = 378 (ES +).

1H NMR (300 MHz, CDCl ₃ ) δ ppm 7.75 (d, 2H), 6.89 (d, 2H), 4.05 (t, 2H), 3.33 (q, 2H), 1.99 (b,

2H), 1.42 (s, 9H), 1.35 (s, 12H).

2-Methylpropan 2-methyl (2-methylbenzyl) -2- {4- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] phenoxy} propyl) carbamate -2-yl 142

142 is prepared according to the procedure of compound 131 from 141 (used crude, 500 mg, 1.32 mmol) and 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b] : 5,4-c '] dipyridine 6 (200 mg, 0.62 mmol), to give the expected product (46 mg, 15%) as a pale yellow solid.

1H NMR (300 MHz, CDCl ₃ ) δ ppm 9.31 (s, 1H), 9.11 (s, 1H), 8.83 (s, 1H), 8.66 (d, 1H), 8.62 (s, 1H), 8.44 (s, 1H), 8.42 (d, 1H), 7.61 (d, 2H), 7.44 (dd, 1H), 7.05 (d, 2H), 4.82 (br, 1H), 4.11 (t, 2H), 3.39 (q, 2H); ), 2.04 (p, 2H), 1.47 (s, 9H).

The compound 142 (45 mg, 0.09 mmol) is treated with 0.5 ml of trifluoroacetic acid in dichloromethane (3 ml) at 0 ^° C. and then stirred at 25 ^° C. overnight. The mixture is then cooled to 0 ^° C. and neutralized with a saturated aqueous solution of sodium bicarbonate to give a suspension which is filtered; the precipitate is washed with water and then with dichloromethane and then dried to give 3- {4- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c]] dipyrid-3-yl] phenoxy} propan-1-amine 143 (35 mg, 97%) as an amber yellow solid.

MS: m / z = 396 (ES +)

1H NMR (300 MHz, DMSO -? / 6) δ ppm 9.37 (s, 1H), 9.03 (s, 1H), 8.98 (s, 2H), 8.89 (s, 1H), 8.59 (d, 1H), 8.51 (d, 1H), 7.74 (d, 2H), 7.54 (dd, 1H), 7.10 (d, 2H), 4.09 (t, 2H), 3.14 (m, 2H), 2.73 (br, 1H), 1.86 ( m, 2H).

Example 156: 4- {4-Methyl-5- [6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] idipyridin-3-yl] pyrid-2-yl] piperazine-1-carboxylate 2-methylpropan-2-yl 144

Compound 144 was prepared according to the procedure of compound 114 from 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 6 (150). mg, 0.462 mmol) and 4- [4-methyl-5- (4,4,5,5-tetramethyl- [1,2,3] dioxaborolan-2-yl) -pyridin-2-yl] -piperazine- 1-carboxylic acid tert-butyl ester (242 mg, 0.60 mmol) to give the expected compound (120 mg, 50%) as a brown solid.

MS: m / z = 522 (ES +).

1H NMR (300 MHz, DMSO -? / 6)? Ppm 12.37 (s, 1H), 9.36 (s, 1H), 9.05 (s, 1H), 8.95 (s, 1H), 8.73 (s, 1H), 8.60. (d, 1H), 8.58 (s, 1H), 8.50 (m, 1H), 8.09 (s, 1H), 7.54 (dd, 1H), 6.89 (s, 1H), 3.56 (m, 4H), 3.46 ( m, 4H), 2.30 (s, 3H), 1.44 (s, 9H).

Example 157: 3- [4-methyl-6- (piperazin-1-yl) pyrid-3-yl] -6- (pyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-dipyridine 145

Compound 145 was prepared according to the procedure of compound 115 from compound 144 (60 mg, 0.115 mmol), to give the expected product (hydrochloride, 4 HCl), 65 mg, 100%) as a yellow solid. .

MS: m / z = 422 (ES +).

1H NMR (300 MHz, DMSO -? / 6) δ ppm 12.78 (s, 1H), 9.54 (s, 1H), 9.45 (br, 2H), 9.26 (s, 1H), 9.17 (s, 1H), 9.14 (s, 1H), 8.90 (d, 1H), 8.81 (s, 1H), 8.69 (s, 1H), 8.12 (t, 2H), 7.23 (s, 1H), 3.93 (br, 4H), 3.25 (s, 1H), br, 4H), 2.38 (s, 3H).

Example 158: 3- [6- (piperazin-1-yl) pyrid-3-yl] -6- (pyrid-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridine 146

Compound 146 was prepared according to the procedure of compound 114 from 3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 6 (150). mg, 0.462 mmol) and 1- [5- (4,4,5,5-tetramethyl- [1,2,3] dioxaborolan-2-yl) -pyridin-2-yl] -piperazine (175 mg, 0.605). mmol), to give the expected compound (172 mg, 92%) as a brown solid.

MS: m / z = 408 (ES +).

1H NMR (300 MHz, DMSO -? / 6) δ ppm 12.32 (br, 1H), 9.37 (s, 1H), 9.03 (s, 1H), 8.99 (s, 1H), 8.95 (s, 1H), 8.90 (s, 1H); (s, 1H), 8.60 (t, 1H), 8.58 (s, 1H), 8.51 (m, 1H), 8.00 (d, 1H), 7.55 (dd, 1H), 6.98 (d, 1H), 3.49 ( t, 4H), 2.81 (t, 4H).

Example 159: 3-Fluoro-6- (5-methoxypyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridine Step 1: 2 ', 5'-dichloro-5-fluoro [3,4 '] bipyridinyl-2-ylamine 147

580 mg of 2-amino-3-bromo-5-fluoropyridine, 1.04 g of 2,5-dichloro-4-trimethylstannanylpyridine 32, 246 mg of tetrakis (triphenylphosphine) palladium (0) are placed in a reactor. and 122 mg of copper (I) iodide in 10 ml of 1,4-dioxane, sealed the tube and subjected to microwave irradiation for 1 h at 125 ^° C. The reaction mixture is filtered through a 0.45 μm frit then washed with dichloromethane. After concentration under reduced pressure, the residue obtained is purified by chromatography on a silica column, eluting with a 100: 0 to 95: 5 mixture of dichloromethane: methanol and then taken up in ethyl acetate. After filtration through a 0.45 μm frit and washing with diethyl ether, 712 mg of 2 ', 5'-dichloro-5-fluoro [3,4'] bipyridinyl-2-ylamine 147 are obtained in the form of a beige solid.

UPLC-MS-DAD-ELSD (LS): Tr (min) = 0.96; (M + H) (+): 258 (+) / 260 (+) / ... (presence of 2 chlorine atoms).

Step 3: 5'-Chloro-5-fluoro-2'-methoxy- [3,4 '] bipyridinyl-2-ylamine 148

In a reactor, 1.6 g of 2 ', 5'-dichloro-5-fluoro [3,4'] bipyridinyl-2-ylam 147 is placed in 10 ml of methanol and then 670 mg of sodium methoxide, sealed on tube and submits to microwave irradiation 1 h at 100 ^° C. The reaction mixture is filtered on a 0.45 μm frit then washed with dichloromethane and concentrated under reduced pressure. The residue is taken up in dichloromethane and in water. After decantation, the organic phase is dried over magnesium sulphate, filtered and then concentrated under reduced pressure to give 1.3 g of 5'-chloro-5-fluoro-2'-methoxy- [3,4 '] bipyridinyl-2 148.

UPLC-MS-DAD-ELSD (LS): Tr (min) = 0.93; (M + H) (+): 254 (+) / ... (presence of a chlorine atom).

Step 4: 3-Fluoro-6-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridine 149

In a tube, 99 mg of (R) - (-) - 1 - [(S) -2-

(dicyclohexylphosphino) ferrocenyl] ethylditerbutylphosphine and 36.3 mg of palladium (II) acetate in 1 ml of anhydrous 1,4-dioxan, under an argon atmosphere and stirred for 10 min at 40 ^° C.

In a reactor, 410 mg of 5'-chloro-5-fluoro-2'-methoxy- [3,4 '] bipyridinyl-2-ylamine 148 and 725 mg of potassium tert-butoxide in 4 ml of water are placed under argon. -dioxan anhydrous then add the previously prepared solution, sealed the tube and subjected to microwave irradiation for 2 h at 120 ^° C. The reaction mixture is filtered on a 0.45 μm frit, washed with dichloromethane and the filtrate obtained is concentrated under reduced pressure. The residue is taken up in ethyl acetate and in water. After decantation, the organic phase is dried over magnesium sulfate, filtered and concentrated under reduced pressure. After trituration in ethyl acetate followed by filtration under vacuum, 350 mg of 3-fluoro-6-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridine 149 are obtained. yellow solid form.

UPLC-MS-DAD-ELSD (LS): Tr (min) = 0.75; (M + H) (+): 218 (+); (M-H) (-): 216 (-). Step 5: 3-Fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-ol 150

In a reactor, 900 mg of 3-fluoro-6-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridine 149 is placed in 6 ml of acetic acid and 4 ml of a solution. aqueous solution of 37% hydrochloric acid, sealed the tube and subjected to microwave irradiation for 3 h at 130 ^° C. The reaction mixture is filtered under vacuum and then washed with diethyl ether to give, after drying, 1.0 g of 3-fluoro-9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-6-ol 150 as a yellow solid.

UPLC-MS-DAD-ELSD (LS): Tr (min) = 0.41; (M + H) (+): 204 (+); (MH) (-): 202 (-). Step 6: 3-Fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl trifluoromethanesulfonate

A mixture of 1 g of 3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-ol 150 in 20 ml of pyridine and 5.8 ml of triflic anhydride is stirred. min at room temperature. The reaction mixture is poured over ethyl acetate and saturated aqueous bicarbonate solution. After decantation, the organic phase is dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue is purified by chromatography on a column of silica eluting with a mixture of heptane: ethyl acetate 100: 0 to 0: 100 to give 828 mg of 3-fluoro-9H-pyrrolo [2,3-b: 5 trifluoromethanesulfonate , 4-c '] dipyridin-6-yl 151 as a beige solid.

UPLC-MS-DAD-ELSD (LS): Tr (min) = 1.22; (M + H) (+): 336 (+); (M-H) (-): 334 (-). Step 7: 3-Fluoro-6- (5-methoxypyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 152

In a reactor, 100 mg of 3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl trifluoromethanesulfonate 151, 105 mg of 3-methoxy-5-pyridineboronic acid are placed in a reactor. pinacol ester, 292 mg of cesium carbonate, 11 mg of 1,1-bis (diphenylphosphino) ferrocenedichloropalladium (II) in 8 ml of 1,4-dioxane and 2 ml of water, sealed the tube and subjected to micro-irradiation. wave 30 min at 125 ⁰ C. the reaction mixture is poured onto water and ethyl acetate. After decantation, the organic phase is dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue is purified by chromatography on a silica column eluting with pure ethyl acetate to give 65 mg of 3-fluoro-6- (5-methoxypyridin-3-yl) -9H-pyrrolo [2,3-b] : 5.4-c '] dipyridine 152 as a yellow solid.

IH NMR (400MHz, DMSO -? / 6) δ ppm 3.95 (s, 3H) 8.05 (dd, J = 2.8, 1.8Hz, 1H) 8.31 (d, J = 2.7Hz, 1H) 8.64 - 8.66 (m, 2H) 8.93 (d, J = LO Hz, 1H) 8.95 (d, J = 17 Hz, 1H) 9.05 (d, J = 1Hz Hz, 1H) 12.39 (brs. , 1H). LC-MS (7 min): Tr (min) = 2.68; [M + H] ⁺ : m / z 295; [MH] ^- : m / z 293.

Example 160: 3-Fluoro-6- (4-methoxypyridin-3-yl) -9H-pyrrolor2,3-b: 5,4-cipyridine 153

Analogously to compound 152, 10 mg of 3-fluoro-6- (4-methoxypyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 153 are obtained from 100 mg of 3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl trifluoromethanesulfonate 151 and 68 mg of 4-methoxy-3-pyridineboronic acid.

1H NMR (400MHz, DMSO -? / 6) δ ppm 3.97 (s, 3H) 7.22 (d, J = 5.9Hz, 1H) 8.47 (d, J = 5.9Hz, 1H)

8.62 - 8.64 (m, 2H) 8.73 (dd, J = 8.9, 2.8 Hz, 1H) 8.84 (s, 1H) 9.03 (d, J = 1.0 Hz, 1H) 12.31 (brs, 1

H).

LC-MS (7 min): Tr (min) = 2.19; [M + H] ⁺ : m / z 295; [MH] ^- : m / z 293.

Example 161: 3-Fluoro-6-r 5- (methylsulfanyl) pyrid-3-yl-9H-pyrrolor2,3-b: 5,4-cidipyridine 154

In a similar manner to compound 152, 50 mg of 3-fluoro-6- [5- (methylsulfanyl) pyridin-3-yl] -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 154 are obtained from 100 mg of 3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl trifluoromethanesulfonate 151 and 141 mg of 5- (methylthio) pyridine-3- acid boronic acid.

1H NMR (400MHz, DMSO -? / 6) δ ppm 2.64 (s, 3H) 8.36 (t, J = 2.1Hz, 1H) 8.49 (d, J = 2.2Hz, 1H) 8.62 - 8.67 (m) , 2H) 8.94 (d, J = 1.0Hz, 1H) 9.05 (d, J = 1.0Hz, 1H) 9.11 (d, J = 2.0 Hz, 1H) 12.37 (brs, 1H) . UPLC-SQD: Tr (min) = 0.67; [M + H] ⁺ : m / z 311; [MH] ^- : m / z 309.

Example 162: 3-Fluoro-6- (thiophen-3-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridine 155

Analogously to compound 152, 89 mg of 3-fluoro-6- (thiophen-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 155 are obtained from 150 mg of 3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl trifluoromethanesulfonate and 86 mg of thiophenyl-3-boronic acid. 1H NMR (400 MHz, DMSO -? / 6)? Ppm 7.67 (dd, J = 3.1 and 5.1 Hz, 1H); 7.80 (dd, J = 1.3 and 5.1 Hz, 1H); 8.05 (dd, J = 1.3 and 3.1 Hz, 1H); 8.61 (dd, J = 2.8 and 7.7 Hz, 1H); 8.62 (d, J = 2.8 Hz, 1H); 8.67 (d, J = 1.2 Hz, 1H); 8.93 (d, J = 1.2 Hz, 1H); 12.25 (bs, 1H) LC-MS-DAD-ELSD: 268 (-) = (MH) (-); 270 (+) = (M + H) (+) Tr (min) = 2.79

Example 163: 3-Methoxy-6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridine 161

5-chloro-2-methoxy-4- (trimethylstannanyl) pyridine 156

A mixture of 10 g of 5-chloro-2-methoxypyridine and 220 ml of tetrahydrofuran is cooled to -78 ^° C. and a freshly prepared solution is then added progressively from 14.1 ml of 2,2,6,6-tetramethylpiperidine. in 50 ml of tetrahydrofuran and 36.4 ml of 2.3 N n-butyllithium in hexane. After stirring for 4 h at -78 ^° C., 17.3 g of trimethyltin chloride dissolved in 30 ml of tetrahydrofuran are added to the reaction mixture. The reaction mixture is stirred at ambient temperature for 18 h and then treated with 200 ml of water and 200 ml of 10% aqueous ammonium chloride solution and extracted with 500 ml and then 200 ml of ethyl acetate. The combined organic phases are dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure. The residue is purified by column chromatography on silica eluting with dichloromethane to give 17.7 g of 5-chloro-2-methoxy-4- (trimethylstannanyl) pyridine 156 as a colorless oil.

UPLC-MS-DAD-ELSD: Tr (min) = 1.24; [M + H] ⁺ : m / z 308.

1H NMR (400MHz, DMSO -? / 6)? Ppm: 0.16 (t, J = 29.6Hz, 9H) 3.62 (s, 3H) 6.61 (t, J = 20.5Hz, 1H) 7.90 (t, m.p. J = 8.3 Hz, 1H).

Step 2: N- (5'-Chloro-2 ', 5-dimethoxy-3,4'-bipyridin-2-yl) -2,2-dimethylpropanamide 157

1.67 g of N- (3-iodo-5-methoxypyridin-2-yl) -2,2-dimethylpropanamide 3g and 2.00 g of 5-chloro-2-methoxy-4 are placed under argon in a reactor. - (trimethylstannanyl) pyridine 156, 404 mg of tetrakis (triphenylphosphine) palladium (0) and 200 mg of copper iodide in 15 ml of 1,4-dioxane and subjected to microwave irradiation for 1 hour at 120 ^° C. 202 mg of tetrakis (triphenylphosphine) palladium (0) and 100 mg of copper iodide are added and subjected again to microwave irradiation for 1 h at 120 ^° C. After 60 h at 25 ^° C., 100 mg is added. tetrakis (triphenylphosphine) palladium (0), 50 mg of copper iodide and 0.50 g of stannylated derivative and subjected to microwave irradiation for 1 h at 120 ^° C.

The reaction mixture is poured into water and ethyl acetate and the suspension obtained is filtered on celite. After decantation, the aqueous phase is extracted with ethyl acetate. The combined organic phases are dried over magnesium sulphate, filtered and then concentrated under reduced pressure. The residue is purified by chromatography on a silica column, eluting with a mixture of heptane: ethyl acetate, 50: 50 to 0: 100 to give 1.28 g of N- (5'-chloro-2 ', 5-dimethoxy-3,4'-bipyridin-2-yl) -2, 2-dimethylpropanamide 157 as a pale yellow solid.

UPLC-MS-DAD-ELSD (LS): Tr (min) = 1.11; (M + H) (+): 350 (+) / 352 (+), presence of a chlorine atom.

Step 3: 3,6-Dimethoxy-9H-pyrrolo [2,3-b: 5,4-c '] dipyridine 158

In a tube, 54 mg of palladium acetate and 152 mg of (R) - (-) - 1 - [(S) -2- (dicyclohexylphosphino) ferrocenyl] ethylditerbutylphosphine are placed under argon in 2 ml of 1,4- dioxane and stirred for 10 min at 40 ⁰ C the solution which is then added to the suspension of 1.20 g of N- (5'-chloro-2 ', 5-dimethoxy-3,4'-bipyridin-2-yl) ) -2,2-dimethylpropanamide 157 and 770 mg of potassium tert-butoxide in 1.75 ml of 1,4-dioxane. The reaction mixture is subjected to microwave irradiation for 30 min at 130 ^° C.

The reaction mixture is taken up in ethyl acetate and filtered through Celite then washed 3 times with water. The organic phase is dried over magnesium sulphate, filtered and then concentrated under reduced pressure. The residue is purified by chromatography on a silica column eluting with heptane: ethyl acetate 50: 50 to 0: 100 to give 417 mg of 3,6-dimethoxy-9H-pyrrolo [2,3-b: 5 4-c '] dipyridine as a yellow solid 158.

UPLC-MS-DAD-ELSD (LS): Tr (min) = 0.73; (M + H) (+): 230 (+). Step 4: 3-Methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-ol 159

In a reactor, 700 mg of 3,6-dimethoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridine 158 are placed in 8.1 ml of acetic acid and 2.7 ml of ethyl acetate. concentrated hydrochloric acid and subjected to microwave irradiation for 2.5 h at 130 ⁰ C. The reaction medium is left for 16 h at 25 ⁰ C and then filtered to give 810 mg of 3-methoxy-9H-pyrrolo [2,3 -b: 5,4-c '] dipyridin-6-ol as an ocher solid 159.

UPLC-MS-DAD-ELSD (LS): Tr (min) = 0.46; (M + H) (+): 216 (+).

3-Methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl trifluoromethanesulfonate

To a solution of 860 mg of 3-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-ol in 40 ml of pyridine under argon is added 0.65 ml of anhydride. trifluoromethanesulfonic. After 30 min at 25 ^° C., 0.65 ml of trifluoromethanesulphonic anhydride are added, the mixture is stirred for 30 min and then the reaction medium is concentrated. This is taken up in ethyl acetate and then washed 3 times with a 5% aqueous ammonia solution. The combined aqueous phases are extracted twice with ethyl acetate and the combined organic phases are dried over magnesium sulfate, treated with carbon black, filtered through celite and then concentrated under reduced pressure to give 941 mg of trifluoromethanesulphonate of 3- methoxy-9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-6-yl 160 as an ocher solid.

UPLC-MS-DAD-ELSD (LS): Tr (min) = 1.26; (M + H) (+): 348 (+).

Step 6: 3-Methoxy-6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolor2,3-b: 5,4-cidipyridine 161

In a reactor, 66 mg of 3-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl trifluoromethanesulphonate are placed under argon. 160.27 mg of l-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazole 5 mg of 1,1-bis (diphenylphosphino) ferrocenedichloropalladium (II) in 0.69 ml of 1, 4-dioxane and 0.275 ml of 1.5 M aqueous cesium carbonate solution and subjected to microwave irradiation for 30 min at 150 ^° C.

The reaction mixture is taken up in ethyl acetate and filtered on celite then washed with water. The organic phase is dried over magnesium sulfate, treated with carbon black, filtered on celite and then concentrated under reduced pressure to give 12 mg of 3-methoxy-6- (1-methyl-1H-pyrazol-4-yl) -9H pyrrolo [2,3-b: 5,4-c '] dipyridine 161 in the form of a brown solid.

1H NMR (400 MHz, DMSO -? / 6) δ ppm 3.91 (s, 3H); 3.93 (s, 3H); 7.97 (s, 1H); 8.18 (s, 1H); 8.26 (d, J = 2.7 Hz, 1H); 8.35 (d, J = 2.7 Hz, 1H); 8.40 (bs, 1H); 8.80 (d, J = 1.0 Hz, 1H); 11.83 (broad s, 1 H). UPLC-SQD: Tr (min) = 0.42; [M + H] ⁺ : m / z 280; [MH] ^": m / z 278.

Example 164: N, N-diethyl-2- [4- (3-methoxy-9H-pyrrolo [2,3-b: 5,4-cidipyridin-6-yl] -3,5-dimethyl-1H-pyrazol-1 -Syllethanamine 162

In a reactor, 52 mg of 3-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl trifluoromethanesulfonate, 160.53 mg of boronic ester 109.5 are placed under argon. , 5 mg of 1,1 '- bis (diphenylphosphino) ferrocenedichloropalladium (II) in 0.75 ml of 1,4-dioxane and 0.30 ml of 1.5 M aqueous cesium carbonate solution and then subjected to microbiological irradiation. wave for 30 min at 150 ^° C.

The reaction mixture is treated with water and extracted with a mixture of ethyl acetate: THF, 80:20. The combined organic phases are dried over magnesium sulphate, treated with carbon black, filtered on celite and then concentrated under reduced pressure. . The residue is purified by chromatography on a silica column, eluting with a dichloromethane: methanol mixture, 80:20 to give 6 mg of N, N-diethyl-2- [4- (3-methoxy-9H-pyrrolo [2,3 -b: 5,4-c '] dipyridin-6-yl) -3,5-dimethyl-1H-pyrazol-1-yl] ethanamine 162.

1H NMR (400 MHz, DMSO -? / 6) δ ppm 0.95 (t, J = 1, 1 Hz, 6H); 2.30 (s, 3H); 2.42 (s, 3H); 2.50 to 2.55 (partially masked m, 4H); 2.75 (t, J = 6.7 Hz, 2H); 3.92 (s, 3H); 4.06 (t, J = 6.7 Hz, 2H); 8.10 (s, 1H); 8.34 (d, J = 2.9 Hz, 1H); 8.39 (d, J = 2.9 Hz, 1H); 8.89 (s, 1H); 11.84 (wide, 1H). UPLC-SQD: Tr (min) = 0.36; [M + H] ⁺ : m / z 393; [MH] -: m / z 391.

Example 165: N - [2- (dimethylamino) ethyl] -2- [4- (3-methoxy-9H-pyrrolo [2,3-b: 5,4-cidipyridin-6-yl] -1H-pyrazol-1-yl] acetamide 164

Etap_eJ _. N- [2- (dimethylamino) ethyl] -2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazol-1-yl] acetamide 163

To a solution of 120 μl of N, N-dimethylethylenediamine in 3 ml of toluene under argon at 15 ^° C. is added dropwise 0.5 ml of 2M trimethylaluminum solution in toluene. After 5 min at 20 ^° C., the reaction medium is treated with a solution of 280 mg of 1- (ethoxycarbonylmethyl) -1H-pyrazole-4-boronic acid, pinacol ester in 1.5 ml of toluene. The reaction medium is stirred for 1 h at 20 ^° C. and then poured into 15 ml of 1M aqueous solution of sodium potassium tartrate and then extracted with twice 20 ml of dichloromethane. The combined organic phases are dried over magnesium sulphate, filtered and then concentrated and dried under reduced pressure to give 125 mg of N- [2- (dimethylamino) ethyl] -2- [4- (4,4,5,5-tetramethyl) -1,2,2-dioxaborolan-2-yl) -1H-pyrazol-1-yl] acetamide 163 as a pale yellow oil.

LC-MS (7 min): Tr (min) = 2.22; [M + H] ⁺ : m / z 323.

In a reactor, 52 mg of 3-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl trifluoromethanesulfonate are placed under argon 160.53 mg of N- [2- ( dimethylamino) ethyl] -2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazol-1-yl] acetamide 163, 7 mg of 1, 1 '- bis (diphenylphosphino) ferrocenedichloropalladium (II) in 0.75 ml of 1,4-dioxane and 0.30 ml of 1.5 M aqueous solution of cesium carbonate and subjected to microwave irradiation for 45 min at 150 ⁰ C. the reaction mixture is concentrated and then the residue obtained is taken up in DMF, added silica, concentrated under reduced pressure to give a solid deposit that is purified by chromatography on silica column, eluting with dichloromethane: methanol: ammonia concentrated, 80: 20: 1 to give 25 mg of N- [2- (dimethylamino) ethyl] -2- [4- (3-methoxy-9H-pyrrolo [2,3-b: 5,4-c]] dipyridin-6-yl) -1H-pyrazol-1-yl] acetamide 164 as a brown solid.

1H NMR (400 MHz, DMSO -? / 6)? Ppm 2.56 to 2.69 (m, spread, 6H); 2.86 to 3.04 (plated m, 2H); 3.37 at 3.45 (m spread, 2H); 3.93 (s, 3H); 4.90 (s, 2H); 8.02 (s, 1H); 8.23 (s, 1H); 8.28 (d, J = 2.9 Hz, 1H); 8.29 to 8.33 (m spread, 1H); 8.36 (d, J = 2.9 Hz, 1H); 8.44 (s, 1H); 8.80 (s, 1H); 9.58 to 10.29 (m spread, 1H); 11.89 (wide, 1H). UPLC-SQD: Tr (min) = 0.31; [M + H] ⁺ : m / z 394; [MH] ^" : m / z 392

Example 166: N, N-diethyl-3-r4- (3-methoxy-9H-pyrrolor2,3-b: 5,4-cidipyridin-6-yl) -1H-pyrazol-1-yllpropan-1-amine 165

Step 1

In a reactor, 37 mg of 3-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl trifluoromethanesulphonate (37 mg), 36 mg of N, N-diethyl- 3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazol-1-yl] propan-1-amine 110, 5 mg of 1.1 bis (diphenylphosphino) ferrocenedichloropalladium (II) in 0.50 ml of 1,4-dioxane and 0.21 ml of 1.5 M aqueous solution of cesium carbonate and then subjected to microwave irradiation for 45 min at 150 ^° C. C. The reaction mixture is concentrated then the residue obtained is taken up in DMF, added with silica, concentrated under reduced pressure to give a solid deposit which is purified by chromatography on a silica column, eluting with a dichloromethane: methanol: concentrated ammonia mixture. 80: 20: 1 to give 18 mg of N, N-diethyl-3- [4- (3-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) 1H-pyrazol-1-yl] propan-1-amine 165. IH NMR (400 MHz, DMSO -? / 6) δ ppm 0.90 to 1.13 (m spread, 6H); 1.92 to 2.09 (m spread, 2H); 2.35 to 3.20 (m partially masked, 6H); 3.93 (s, 3H); 4.15 to 4.25 (wide m, 2H); 8.02 (s, 1H); 8.24 (s, 1H); 8.27 (d, J = 2.9 Hz, 1H); 8.35 (d, J = 2.9 Hz, 1H); 8.42 (bs, 1H); 8.81 (d, J = 1, 2 Hz, 1H); 11.85 (wide, 1H). UPLC-SQD: Tr (min) = 0.36; [M + H] ⁺ : m / z 379.

Example 167: 2-Methylpropan-2-yl {5-r4- (3-methoxy-9H-pyrrolor-2,3-b: 5.4-c-dipyridin-6-yl) -1H-pyrazol-1-yllpentylcarbamate

Step 1: 2-Methylpropan-2-methyl {5- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazol-1-yl] pentyl} carbamate -yle 166

In a microwave reactor of suitable size are introduced 100 mg of 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazole, 137 mg of N- (5-bromopentyl) -2,2-dimethylpropanamide, 671 mg of cesium carbonate and 2.0 ml of tetrahydrofuran. The mixture is irradiated for 1 hour at 130 ^° C. The reaction medium is concentrated and then taken up in ethyl acetate and washed twice with water. The organic phase is dried over magnesium sulphate, filtered and then concentrated under reduced pressure to give 145 mg of {5- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) 1-methylpropan-2-yl-1H-pyrazol-1-yl] pentyl} carbamate as a colorless oil and used crude in the next step.

UPLC-SQD: Tr (min) = 1.03; [M + H] ⁺ : m / z 380.

Step 2: {5- [4- (3-Methoxy-9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-6-yl) -1H-pyrazol-1-yl] pentyl} carbamate 2-methylpropan-2-yl 167

In a reactor, 70 mg of 3-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl trifluoromethanesulfonate are placed under argon. 160.91 mg of {5- [4- (9 mg) 1-methyl-2-methylpropan-2-yl (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazol-1-yl] pentyl} carbamate, 9 mg of 1, 1 '- bis (diphenylphosphino) ferrocenedichloropalladium (II) in 1.0 ml of 1,4-dioxane and 0.4 ml of 1.5 M aqueous solution of cesium carbonate and subjected to microwave irradiation for 45 min at 150 ⁰ C. the reaction mixture is concentrated and then the residue obtained is taken up in DMSO and purified by HPLC in acidic medium to give 32 mg of {5- [4- (3-methoxy-9H-pyrrolo [2,3-b: 2-Methylpropan-2-yl-5,4-c '] dipyridin-6-yl) -1H-pyrazol-1-yl] pentyl} carbamate 167 as a salt with trifluoroacetic acid. 1H NMR (400 MHz, DMSO -? / 6) δ ppm 1.19 to 1.29 (m, 2H); 1.35 (s, 9H); 1.37 to 1.46 (m, 2H); 1.78 to 1.88 (m, 2H); 2.87 to 2.93 (m, 2H); 3.95 (s, 3H); 4.19 (t, J = 6.9 Hz, 2H); 6.81 (t, J = 5.6 Hz, 1H); 8.05 to 8.17 (m, 1H); 8.30 to 8.42 (m, 2H); 8.45 to 8.58 (m, 1H); 8.60 to 8.79 (m spread, 1H); 8.85 to 8.95 (m, 1H); 11.85 to 12.74 (spread m, 1H).

Example 168: 5- [4- (3-Methoxy-9H-pyrrolo [2,3-b: 5,4-cidipyridin-6-yl] -1H-pyrazol-1-yl) pentan-1-amine

To 150 mg of the product of compound 167 are added 2 ml of 4 N solution of hydrochloric acid in 1,4-dioxane. The reaction medium is stirred under ultrasound at 25 ^° C. for 1 h and then filtered; the solid obtained is rinsed 3 times with ethyl acetate to give 135 mg of 5- [4- (3-methoxy-9H-pyrrolo [2,3-b: 5,4-c]] dipyridin-6 -yl) -1H-pyrazol-1-yl] pentan-1-amine 168 as a hydrochloride and an ocher solid.

1H NMR (400 MHz, DMSO -? / 6) δ ppm 1.29 to 1.41 (m, 2H); 1.55 to 1.68 (m, 2H); 1.79 to 1.94 (m, 2H); 2.72 to 2.84 (m, 2H); 3.97 (s, 3H); 4.25 (t, J = 6.7 Hz, 2H); 7.72 to 7.92 (m spread, 3H); 8.26 to 8.34 (m wide, 1H); 8.42 to 8.47 (m, 1H); 8.56 to 8.63 (m, 1H); 8.63 to 8.72 (m spread, 1H); 8.89 to 8.93 (m, 1H); 8.95 to 9.10 (m spread, 1H); 12.41 to 13.03 (m spread, 1H). UPLC-SQD: Tr (min) = 0.35; [M + H] ⁺ : m / z 351.

Example 169: 3-Methoxy-6- (1-yl) -2- (1-methylpiperid-2-yl) ethyl-1H-pyrazol-4-yl} -9H-pyrrolor2,3-b: 5.4-dipyridine 170

Step 1: 1-methyl-2- {2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazol-1-yl] ethyl} piperidine 169

In a microwave reactor of suitable size are introduced 388 mg of 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazole, 412 mg of 2- (2-bromoethyl) -1-methylpiperidine, 2.6 g of cesium carbonate and 8 ml of tetrahydrofuran. The mixture is irradiated for 1 hour at 130 ^° C. The reaction medium is diluted with ethyl acetate and washed 3 times with water. The organic phase is dried over magnesium sulphate, filtered and then concentrated under reduced pressure to give 482 mg of 1-methyl-2- {2- [4- (4,4,5,5-tetramethyl) -1,2 dioxaborolan-2-yl) -1H-pyrazol-1-yl] ethyl} piperidine 169 as a colorless oil and used crude in the next step.

UPLC-SQD: Tr (min) = 0.51; [M + H] ⁺ : m / z 320.

In a reactor, 70 mg of 3-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl trifluoromethanesulfonate are placed under argon. 160.91 mg of 1-methyl-2- {2- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazol-1-yl] ethyl} piperidine 169, 9 mg of 1.1 ' bis (diphenylphosphino) ferrocenedichloropalladium (II) in 1.0 ml of 1,4-dioxane and 0.4 ml of 1.5 M aqueous solution of cesium carbonate and then subjected to microwave irradiation for 45 min at 150 ^° C. The reaction mixture is concentrated then the residue obtained is taken up in DMSO and purified by HPLC in an acidic medium to give 32 mg of 3-methoxy-6- {1- [2- (1-methylpiperidin-2-yl) ethyl] 1H-pyrazol-4-yl} -9H-pyrrolo [2,3-b: 5,4-c] dipyridine 170.

1H NMR (400 MHz, DMSO -? / 6) δ ppm 1.04 to 3.58 (m, 14H); 3.93 (s, 3H); 4.24 (m, 2H); 8.02 (s, 1H); 8.26 (d, J = 2.9 Hz, 1H); 8.30 (s, 1H); 8.36 (d, J = 2.9 Hz, 1H); 8.41 (brs, 1H); 8.81 (d, J = 1.2 Hz, 1H); 11.86 (s, 1H). UPLC-SQD: Tr (min) = 0.36; [M + H] ⁺ : m / z 391; [M + 2H] ²⁺ : m / z 196 (base peak).

Example 170: 4- (6-Tri- (prop-2-en-1-yl) -1H-pyrazol-4-yl] -9H-pyrrolo [2,3-b] -5,4-di-dipyridin-4-yl] benzoate methyl 177

Step 1: 5'-Chloro-2 ', 4-dimethoxy-3,4'-bipyridin-2-amine 171

368 mg of 5-chloro-2-methoxy-4- (trimethylstannanyl) pyridine 156, 250 mg of 3-iodo-4-methoxy-pyridin-2-ylamine 3h, 304 mg of cesium fluoride are placed in a tube, 38 mg of copper iodide in 2 ml of dimethylformamide and then 116 mg of tetrakis (triphenylphosphine) palladium (0) and 2 ml of dimethylformamide, sealed the tube and subjected to microwave irradiation at 125 ⁰ C for 2 h. The reaction mixture is filtered on celite, rinsed with 10 ml of ethyl acetate and then washed twice with 10 ml of water. After decantation, the organic phase is dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a silica column eluting with a heptane: ethyl acetate: 50/50 to 0/100 mixture to give 125 mg of 5'-chloro-2,4 'dimethoxy-3,4' bipyridin-2-amine 171 as a white solid.

UPLC-MS-DAD-ELSD: Tr (min) = 0.44; [M + H] ⁺ : m / z 266.

1H NMR (400MHz, DMSO -? / 6)? Ppm: 3.68 (s, 3H) 3.87 (s, 3H) 5.40 (s, 2H) 6.42 (d, J = 5.9Hz, 1H NMR (CDCl3)?

H) 6.72 (d, J = 0.5 Hz, 1H) 7.94 (d, J = 5.9 Hz, 1H) 8.28 (d, J = 0.5 Hz, 1H).

Step 2: 4,6-Dimethoxy-9H-pyrrolo [2,3-b: 5,4-c '] dipyridine 172

In a 2 ml tube, 10.3 mg of (R) - (-) - 1 - [(S) -2- (dicyclohexylphosphino) ferrocenyl] ethylditerbutylphosphine and 3.8 mg of acetate are placed under an argon atmosphere. of palladium (II) in 0.35 ml of anhydrous 1,4-dioxane, and stirred for 10 min at 35 ^° C.

In a 2 ml reactor, 45 mg of 5'-chloro-2 ', 4-dimethoxy-3,4'-bipyridin-2-amine 171 and 38 mg of potassium tert-butoxide in 0.35 ml of potassium are placed under argon. Anhydrous 1,4-dioxane, then the previously prepared solution and 0.20 ml of 1,4-dioxane are added, the tube is sealed and subjected to microwave irradiation for 1 hour at 130 ^° C. The reaction mixture is diluted with a mixture of dichloromethane: 90:10 methanol and then filtered. After concentration under reduced pressure, the residue is purified by chromatography on a silica column, eluting with a dichloromethane: methanol mixture 98: 2 to 94: 6 to give 28.5 mg of 4,6-dimethoxy-9H-pyrrolo [2, 3-b: 5,4-c '] dipyridine 172 as a yellow solid.

UPLC-MS-DAD-ELSD: Tr (min) = 0.40; [M + H] ⁺ : m / z 230.

1H NMR (400MHz, DMSO -? / 6)? Ppm: 3.89 (s, 3H) 4.09 (s, 3H) 6.85 (d, J = 5.9Hz, 1H)

J = LOHz, 1H) 8.39 - 8.42 (m, 2H) 11.70 (brs, 1H).

Step 3: 9H-pyrrolo [2,3-b: 5,4-c '] dipyridine-4,6-diol hydrochloride

In a 20 ml reactor, 1.52 g of 4,6-dimethoxy-9H-pyrrolo [2,3-b: 5,4-c '] dipyridine 172 are placed in 22.1 ml of acetic acid and 7 3 ml of a 37% solution of hydrochloric acid, sealed the tube and subjected to microwave irradiation for 2 h at 140 ^° C. After concentration of the reaction mixture, the solid obtained is slurried in twice 25 ml of diethyl ether and then dried under reduced pressure for 18 h to give 1.72 g of 9H-pyrrolo [2,3-b: 5,4-c '] dipyridine-4,6-diol hydrochloride as a dark beige solid.

UPLC-MS-DAD-ELSD: Tr (min) = 0.14; [M + H] ⁺ : m / z 202; [MH] -: m / z 200.

IH NMR (400 MHz, DMSO -? / 6) δ ppm: 6.48 (m, 1H) 7.62 (s, 1H) 8.06 (d, J = 7.1 Hz, 1H) 8.34 (s,

1H) 12.48 (brs, 1H)

Step 4: 9H-Pyrrolo [2,3-b: 5,4-c '] dipyridine-4,6-diyl bis (trifluoromethanesulfonate) 174

A mixture of 1.72 g of 9H-pyrrolo [2,3-b: 5,4-c '] dipyridine-4,6-diol hydrochloride in 35 ml of pyridine and 9.1 ml of triethylamine is cooled to room temperature. 5 ⁰ C followed by addition of 2.8 ml of trifluoromethanesulfonic anhydride. The reaction mixture is stirred at 0-5 ^° C. for 1 h and then poured into a mixture of 200 ml of water and 50 ml of saturated aqueous sodium chloride solution and extracted with 250 ml of ethyl acetate. After decantation, the aqueous phase is extracted with 200 ml of ethyl acetate and the organic phases are combined and concentrated in vacuo. The residue is taken up in a mixture of 100 ml of 80/20 dichloromethane: ethyl acetate mixture, supplemented with 6.0 g of silica and concentrated under reduced pressure. The solid deposit formed is purified by chromatography on a silica column, eluting with a dichloromethane: ethyl acetate mixture 100: 0 to 80: 20 to give 124 mg of 9H-pyrrolo [2,3-b: bis (trifluoromethanesulfonate): 5,4-c '] dipyridine-4,6-diyl 174 as a rust solid.

UPLC-MS-DAD-ELSD: Tr (min) = 4.81; [M + H] ⁺ : m / z 466; [MH] ^- : m / z 464. 1H NMR (400 MHz, DMSO -? / 6)? Ppm: 7.59 (d, J = 5.6 Hz, 1H) 7.96 (s, 1H) 8.E (d, J = 0.7Hz, 1H) 8.89 (d, J = 5.6Hz, 1H) 13.32 (brs, 1H).

In a microwave reactor of suitable size are introduced under argon 158 mg of 9H-pyrrolo [2,3-b: 5,4-c '] dipyridine-4,6-di-di (trifluoromethanesulfonate) 174, 89 mg of boronate, 166 mg of cesium carbonate, 1.55 ml of dioxane, 25 mg of 1,1 '- bis (diphenylphosphino) ferrocenedichloropalladium (II) and 0.15 ml of water. The mixture is irradiated 15 min. 140 ⁰ C. the suspension obtained is diluted with ethyl acetate and washed with a saturated aqueous solution of ammonium chloride. The aqueous phase is extracted with ethyl acetate and the organic phases are combined, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue is purified by chromatography on a silica column eluting with a dichloromethane: ethyl acetate mixture, 80:20 to 50:50 to give 30 mg of 175 as a yellow solid.

UPLC-SQD: Tr (min) = 1.08; [M + H] ⁺ : m / z 452; [MH] ^" : m / z 450. Step 6:

621 mg of 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazole are introduced into a microwave reactor of appropriate size, 2.08 g of cesium carbonate, 16 ml of dimethylformamide, and 0.55 ml of allyl bromide. The mixture is irradiated for 1 hour at 100 ^° C. The suspension obtained is diluted with ethyl acetate and washed with an aqueous solution of sodium bicarbonate. The aqueous phase is extracted with ethyl acetate and the organic phases are combined, dried over magnesium sulphate, filtered and then concentrated under reduced pressure to give 292 mg (39%) of 1- (prop-2-enyl) - 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazole 176.

LC-MS (7 min): Tr (min) = 3.68; [M + H] ⁺ : m / z 235. Step 7:

28 mg of the product of step 175, 22 mg of boronate prepared in step 6176, 30 mg of cesium carbonate, 0.45 ml of dioxane are introduced into an appropriately sized microwave reactor in argon. 5 mg of 1-r-bis (diphenylphosphino) ferrocenedichloropalladium (II) and 50 μl of water. The mixture is irradiated for 30 min at 130 ^° C. 4 mg of 1,1 '-bis (diphenylphosphino) ferrocenedichloropalladium is added. (II), 15 mg of boronate prepared in step 6 176 and 0.1 ml of dioxane and irradiated again for 1 h at 140 ^° C. The suspension obtained is diluted with ethyl acetate and washed with water. 'water. The aqueous phase is extracted with ethyl acetate and the organic phases are combined, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue is purified by chromatography on a silica column, eluting with a dichloromethane: methanol mixture, 100: 0 to 96: 4 to give 8 mg of 4- {6- [1- (prop-2-en-1-yl) Methyl-1H-pyrazol-4-yl] -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl} benzoate 177 as an ocher solid.

1H NMR (400 MHz, DMSO -? / 6)? Ppm: 3.96 (s, 3H); 4.77 (d, J = 5.7 Hz, 2H); 5.15 (d, J = 16.9 Hz, 1H); 5.21 (broad d, J = 9.8 Hz, 1H); 5.96 to 6.11 (m, 1H); 7.28 (d, J = 4.9 Hz, 1H); 7.61 (s, 1H); 7.67 (s, 1H); 7.93 (d, J = 8.3 Hz, 2H); 8.00 (s, 1H); 8.27 (d, J = 8.3 Hz, 2H); 8.65 (d, J = 4.9 Hz, 1H); 8.90 (s, 1H); 12.34 to 12.41 (s wide, 1H). LC-MS (7 min): Tr (min) = 3.19; [M + H] ⁺ : m / z 410; [MH] -: m / z 408.

Example 171: N- {4- (3-Fluoro-6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolor 2,3-b: 5,4-cidipyridin-4-yl] phenylmethanesulfonamide 183

In a 500 ml reactor, 7.6 g of 3-fluoro-6-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridine are placed under argon in 180 ml of dimethylformamide and 2, 38 g of 60% sodium hydride in the oil. After stirring for 3 hours at room temperature are added 13.3 g of para-toluenesulfonyl chloride dissolved in 20 ml of dimethylformamide. The reaction medium is stirred for 3 h at room temperature and then poured into a 5% aqueous solution of sodium hydrogencarbonate. The crude product is recovered by filtration and dried in air. After redissolving in dichloromethane, 24 g of silica are added and the whole is concentrated under reduced pressure. Purification by chromatography on a silica column eluting with a 100: 0 to 95: 5 dichloromethane: methanol mixture gives 11.6 g 3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6-methoxy-9H-pyrrolo [2,3-b: 5,4-c '] dipyridine.

UPLC-MS-DAD-ELSD: 372.11 (+) = (M + H) (+) Tr (min) = 1.35; 2nd step

In a dry three-necked and argon, 3.1 ml of diisopropylamine are loaded into 40 ml of tetrahydrofuran. After stirring and cooling to -78 ^° C., 8.1 ml of 2.5 N n-butyllithium in hexane are added dropwise. The reaction mixture is stirred for 15 min at -78 ^° C., then 5.0 g of 3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6-methoxy-9H-pyrrolo [2,3-b: 5 are added. 4-c '] dipyridine 178 in 250 ml of tetrahydrofuran. After stirring for 2 h at -78 ^° C., 5.46 g of iodine in 10 ml of tetrahydrofuran are added. After stirring for 1 h, the reaction mixture is poured into 400 ml of a 10% aqueous solution of ammonium chloride and 250 ml of water, extracted twice with 400 ml of ethyl acetate. The organic phases are washed with an aqueous solution of 5% sodium thiosulfate, dried over sodium sulphate, filtered and concentrated to dryness under reduced pressure. 6.57 g of 3-fluoro-4-iodo-9 - [(4-methylphenyl) sulfonyl] -6-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridine 179 are obtained.

UPLC-MS-DAD-ELSD: 498.01 (+) = (M + H) (+) Tr (min) = 1.43; Step 3

In a microwave reactor of suitable size are introduced 278 mg (0.84 mmol) of 3-fluoro-4-iodo-9 - [(4-methylphenyl) sulfonyl] -6-methoxy-9H-pyrrolo [2, 3-b: 5,4-c '] dipyridine 179, 1.67 mmol of boronate 20b, 77 mg of tetrakis (triphenylphosphine) palladium (O), 273 mg of cesium carbonate, 5.5 ml of dioxane and 1, 3 ml of water. The mixture is irradiated for 1 hour at 120. 3 ml of methanol are added, then the mixture is poured into water (50 ml) and ethyl acetate (100 ml), the phases are separated and the aqueous phase is dissolved. again extracted with 100 mL of ethyl acetate. The combined organic phases are dried over magnesium sulphate, filtered and then concentrated under reduced pressure. The residue is purified by chromatography on silica gel (60 g of gradient silica dichloromethane / ethyl acetate 100/0 to 50/50), one obtains 250 mg (83%) of the expected compound N- [4- (3- 9-fluoro-[(4-methylphenyl) sulfonyl] -6-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} methanesulfonamide 180.

UPLC-MS-DAD-ELSD: 541.14 (+) = (M + H) (+) Tr (min) = 1.31; Step 4

To a solution of 305 mg of N- [4- (3-fluoro-9 - [(4-methylphenyl) sulfonyl] -6-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridine 4-yl] phenyl} -methanesulfonamide 180 in 5.5 ml of acetic acid is added 0.5 ml of a 37% hydrochloric acid solution, the mixture is heated in the microwave for 2 hours. at 120 ^° C., then poured onto a mixture of ethyl acetate and a 5% aqueous solution of potassium carbonate with vigorous stirring, the pH being brought to 7 by addition of an aqueous solution of 5N HCl. After separation of the phases, the organic phase is dried over MgSO 4, filtered and then concentrated under reduced pressure to give 99 mg of N- [4- (3-fluoro-6-hydroxy-9H-pyrrolo [2,3-b: 5, 4-c '] dipyridin-4-yl] phenyl} -methanesulfonamide 181. UPLC-MS-DAD-ELSD: 373.09 (+) = (M + H) (+) Tr (min) = 0.65;

To a suspension of 98 mg N- [4- (3-fluoro-6-hydroxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} -methanesulfonamide 181 in 5 ml of pyridine is added 0.27 ml of trifluoromethanesulphonic anhydride The reaction mixture is stirred for 2 hours and then concentrated under reduced pressure The reaction medium is poured into a mixture of ethyl acetate and a solution 5% aqueous sodium bicarbonate with vigorous stirring After separation of the phases, the organic phase is dried over MgSO 4, filtered and then concentrated under reduced pressure UPLC-MS-DAD-ELSD: 504 = (M + H) (+) Tr (min) = 1.14

The brown solid 182 is loaded into a microwave tube with 20 μmol of 1,1'-bis (diphenylphosphino) ferroocenedichloro palladium (II), 0.89 mmol of cesium carbonate, 4 ml of dioxane and 1 ml of water and 0.52 mmol of 1-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazole. The mixture obtained is irradiated for 1 hour at 120 ^° C., 1 ml of methanol is added, then the mixture is poured into water (25 ml) and ethyl acetate (50 ml), the phases are separated and the mixture is dissolved. The aqueous phase is again extracted with 50 ml of ethyl acetate. The organic phases are combined and dried over magnesium sulfate, filtered and then concentrated under reduced pressure. The residue is purified by chromatography on silica gel (30 g of gradient silica dichloromethane / methanol 100/0 to 90/10), giving 70 mg (62%) of the expected compound N- {4- [3-fluoro-6 (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-4-yl] phenyl} methanesulfonamide 183.

1H NMR (400 MHz, DMSO -? / 6)? Ppm: 3.17 (s, 3H); 3.85 (s, 3H); 7.40 (d, J = 0.9 Hz, 1H); 7.51 (d, J = 8.6 Hz, 2H); 7.59 (s, 1H); 7.69 (d, J = 8.6 Hz, 2H); 7.91 (s, 1H); 8.67 (d, J = 2.5 Hz, 1H); 8.87 (d, J = 0.9 Hz, 1H); 9.92 to 10.24 (m spread, 1H); 12.26 (wide, 1H)

UPLC - SQD: Tr (min) = 0.55; MH + = 437+; MH = 435-

Example 172 (187) and Example 173: (4-methylpiperazin-1-yl) (9H-pyrrolor2,3-b: 5,4-cidipyridin-6-yPmethanone 188

Step 1: 5-chloro-2-cyano-4-trimethylstananyl-pyridine 184

In a dry monocolon and under argon are introduced 5 g of 5-chloro-2-cyanopyridine, 9.35 g of trimethyltin chloride and 200 ml of THF. The mixture is stirred and cooled to -78 ⁰ C, then 19.85 ml of a commercial solution of LDA (2N in toluene) are added dropwise in 45 minutes. The medium turns yellow and then browns. After stirring for 3 h, the reaction medium is hydrolyzed with an ammonium chloride solution, and then the aqueous phase is extracted with ethyl acetate. The organic phase is dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue obtained is purified by chromatography on silica gel using a gradient of 0% to 2% of ethyl acetate in heptane. The fractions containing the expected product are combined and concentrated under reduced pressure to give 3.4 g (31%) of 5-chloro-2-cyano-4-trimethylstanannanylpyridine 184 as a white solid.

UPLC-MS-DAD-ELSD: 302.97 (+) = (M + H) (+) (isotopic profile corresponding to a tin derivative) Tr (min) = 1.39

Step 2: 9H-pyrrolo [2,3-b: 5,4-c '] dipyridine-6-carbonitrile

2.78 g of 2-amino-3-iodopyridine, 3.4 g of 5-chloro-2-cyano-4-trimethylstanannanyl-pyridine 184 and 912 mg of tetrakis ( triphenylphosphine) palladium (0), 451 mg of copper iodide and 15 ml of dioxane. The reaction medium is irradiated for 1 hour at 120 ^° C. and then hydrolyzed with 75 ml of a 10% aqueous solution of sodium bicarbonate and 5 ml of water. The aqueous phase is extracted twice with 50 ml of ethyl acetate, the combined organic phases are then dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue is then crystallized by trituration in heptane. The product 185 recovered by filtration is dissolved in 80 ml of DMSO, then 1.32 g of copper iodide and 14.3 g of potassium carbonate are added. The mixture is heated overnight at 160 ^° C. After cooling, the reaction medium is poured into a mixture of ethyl acetate and 28% aqueous ammonia with vigorous stirring. After stirring for one hour, the phases are separated, the organic phase is dried over MgSO 4, filtered and then concentrated under reduced pressure. The expected product is crystallized by trituration in dichloromethane to give 1.1 g (50% on both stages) of 9H-pyrrolo [2,3-b: 5,4-c] dipyridine-6-carbonitrile.

UPLC-MS-DAD-ELSD: 195 (+) = (M + H) (+) Tr (min) = 0.69

Step 3: 9H-Pyrrolo [2,3-b: 5,4-c '] dipyridine-6-carboxylic acid 187

In a tube for microwave apparatus, 1.1 g of 9H-pyrrolo [2,3-b: 5,4-c '] dipyridine-6-carbonitrile 186 are dissolved in 10 ml of an aqueous solution of acid Hydrochloric acid 6N. The mixture is heated at 140 ^° C. for one hour under a microwave. After cooling, the mixture is taken up in water and ethyl acetate, the precipitate is filtered. The pH of the filtrate is reduced to 4, and the precipitate again formed is also isolated by filtration. Both solids have the same profile in UPLC-MS. 1.03 g (86%) of 9H-pyrrolo [2,3-b: 5,4-c '] dipyridine-6-carboxylic acid 187 is obtained.

UPLC - SQD: Tr (min) = 0.25; MH + = 214+; MH = 212-

1H NMR (400 MHz, DMSO -? / 6) δ ppm: 7.58 (dd, J = 4.8 and 8.0 Hz, 1H); 8.86 to 8.93 (m, 1H); 9.08 to 9.17 (m, 2H); 9.48 (bs, 1H)

In a monocol, 45 mg of 9H-pyrrolo [2,3-b: 5,4-c '] dipyridine-6-carboxylic acid 187 are charged together with 5 mL of thionyl chloride. The mixture is heated overnight under reflux with stirring and then concentrated under reduced pressure. The crude is taken up in 5 ml of dichloromethane, then 215 μl of methylpiperazine are added. After 1 hour, the reaction medium is concentrated in vacuo. The product is purified by preparative HPLC in an acid medium using a water gradient + 0.07% trifluoroacetic acid / acetonitrile + 0.07% trifluoroacetic acid, to give 40 mg (50%) of (4-methylpiperazin-1 -yl) (9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-6-yl) methanone 188.

Mass spectrometry: spectrum produced by chemical ionization (reactant gas: ammonia) on WATERS GCTof (direct introduction without LC): [M + H] +: m / z 296

1H NMR (400 MHz, DMSO -? / 6)? Ppm: 2.87 (s, 3H); 3.05 to 3.67 (m spread, 6H); 4.34-4.80 (m spread, 2H); 7.37 (dd, J = 4.9 and 7.9 Hz, 1H); 8.61 (d, J = 0.7 Hz, 1H); 8.65 (dd, J = 1.8 and 4.9 Hz, 1H); 8.79 (dd, J = 1.8 and 7.9 Hz, 1H); 8.89 (d, J = 0.7 Hz, 1H); 9.62 to 10.06 (m spread, 1H); 12.46 (s, 1 H) The following table shows the correspondence between the compounds described in the above schemes and preparations, and for the compounds which constitute products of formula (I), their respective example numbers from 1 to 173 in the present invention.

In Vitro Biochemical Testing Procedures

The pharmacological properties of the compounds of the invention can be confirmed by a number of pharmacological assays. The following examples of pharmacological assays were carried out with compounds according to the invention.

Example 1

TR-FRET dosage

In order to determine the inhibition of the activity of Pim kinases, the compounds of the invention are tested according to a TR-FRET assay ("Time Resolved-Fluorescence Resonance Energy Transfer", fluorescence energy transfer by resonance in time. resolved) in vitro used routinely. The TR-FRET assay is based on the detection of phosphorylation of the Ser1 12 specific residue in the Bad protein, which has been shown to be a natural substrate of Pim kinases in cells. For the assay, the following reagents are used:

Pim Kinase - Recombinant Full-Length Human Protein Pim-1, Pim-2 or Pim-3

His6 (prepared according to J. Mol Biol (2005) 348, 183-193);

Bad - His6-tagged recombinant full-length human Bad Bad protein (prepared according to J. Mol.

Biol. (2005) 348, 183-193); α-His6-APC - SureLight ™ allophycocyanin-conjugated mouse monoclonal antibody directed against the His6 tag (Perkin Elmer, No. AD0059H, Waltham, Mass., USA); α-P-Bad-Eu - mouse monoclonal antibody (CeIl Signaling Technology # 9296B, Danvers,

Massachusetts, USA) directed against phosphoBad (SerI 12) (7El 1) labeled at the request of

Perkin Elmer with LANCE ™ reagent Eu-Wl 024.

The assay is based on PerkinElmer's LANCE ™ technology: the Eu-labeled antibody binds to phospho-SerI 12 and generates a TR-FRET signal by interaction with PCA-labeled His6 antibody bound to His6 tag of Bad. The TR-FRET signal is detected using a SpectraMax M5 plate reader (Molecular Devices) with the following settings: λex = 340 nm, λem1 = 615 nm, λem2 = 665 nm. The fluorescence signal ratio at 665 nm on fluorescence signal at 615 nm is used as the signal reading for the IC ₅₀ (calculations based on the 4-parameter logistic model). The assay is implemented in a 384-well format; liquid handling is performed at using a Beckman 3000 liquid handling station. Test compounds are tested at 10 concentration points in duplicate; the highest compound concentration is typically 30 μM. The concentration of ATP is 40 μM, which is equivalent to the apparent K _M value.

Example 2

Radiometric binding of filter binding

In order to confirm their potency, the compounds of the invention may be counter-selected using a radiometric filter binding assay. This assay measures the phosphorylation of a synthetic peptide (RSRHS SYPAGT) corresponding to amino acids 107-117 of the mouse Bad protein, which include the Ser1 phosphorylation site 12 (Upstate No. 12-542), in the presence of ³³ P-ATP as second substrate. The reaction is conducted in the same format as the TR-FRET assay described above. In the reaction, the basic substrate peptide binds to the phosphocellulose filter, and the phosphorylation level is quantified by liquid scintillation counting. Again, the concentration of ATP is 40 μM, which is equivalent to the apparent K _M value.

Example 3

Determination of cell viability

Representative compounds of the invention are also screened for their effects on cell proliferation and viability using a variety of tumor cell lines from humans, representative of various pathological indications. These cell lines include:

Hematological cancer models:

TF-I (acute myelogenous leukemia, AML M6 at the time of diagnosis);

KG-I (AML, erythro leukemia evolving in AML);

KG-Ia (AML, subclone derived from immature KG-I);

EOL-I (AML, eosinophilic leukemia);

PL-21 (AML; M3);

ML-2 (AML, T-NHL evolving into T-ALL evolving in AML M4);

HL-60 (AML, M3);

Kasumi-1 (AML);

GDM-I (AML);

K-562 (CML - chronic myelogenous leukemia, blast crisis);

JURL-MK1 (CML blast crisis);

DND-41 (T-ALL - T-cell acute lymphoblastic leukemia);

Jurkat (T-ALL); NALM-6 (B-ALL-ALL to B-cells);

CEM (ALL, ALL lymphosarcoma); Jeko-1 (B-NHL - B-cell non-Hodgkin's lymphoma, large cell variant leukemia-derived mantle cell lymphoma);

WSU-DLCL2 (B-NHL, diffuse large B-cell lymphoma); RL (B-NHL; undifferentiated diffuse); OCI-LyIO (B-NHL); DoHH-2 (B-NHL);

RPMI-8226 (MM - multiple myeloma);

JVM-2 (B-CLL - B-cell chronic lymphocytic leukemia); and JVM-3 (B-CLL) MV4-11 (AML) MOLM1 3 (AML).

Solid tumor models:

HCT-116 (colon cancer);

HT-29 (colon cancer);

HC-15 (colon cancer);

H460 (lung cancer, non-small cell lung cancer);

A375 (melanoma);

B 16F (melanoma);

MDA-Al (breast cancer);

MDA-MB231 (breast cancer);

MDA-MB231 adr (breast cancer);

PANC-I (pancreatic cancer); and

PC-3 (prostate cancer).

In order to measure viability, the tumor cells are incubated in a 96-well or 384-well format for 48, 72 or 96 hours, preferably 72 hours, with a compound of the invention at 3-fold dilutions with in general, nine doses in total, the highest dose being equal to 10 μM or 30 μM. Cell viability is assessed by adding CellTiter-Blue ^® (Promega, Madison, Wisconsin, USA) for 4 hours and end point readings are performed using a SpectraMax Genmini EM plate reader (Molecular Devices, Sunnyvale , California, United States). CellTiter-Blue cell viability assay measures the ability of cultured cells to effect resorption of resazurin, the intensity of the fluorescence signal being directly proportional to the number of living cells. EC ₅₀ represents the concentration of compound that leads to a 50% reduction in proliferative cell viability / expansion.

BIOCHEMICAL RESULTS

The biochemical results are expressed according to the following classification: Class A: IC50 between 1 nM and 100 nM

Class B: IC50 between 100 nM and 1000 nM (or 1 μM)

Class C: IC50 between 1 μM and 5 μM

Class D: IC50 greater than 5μM

BIOCHEMICAL RESULTS OF COMPARATORS CELLULAR RESULTS

Cell proliferation results are expressed according to the following classification

Class A: IC50 between 1 nM and 100 nM

Class B: IC50 between 100 nM and 1000 nM (or 1 μM)

Class C: IC50 between 1 μM and 5 μM

Claims

CLAIMS1 Compounds of general formula (I) below: wherein R3, R4 may be independently of one another:

1. H

2. halogen;

3. CF ₃ ;

4. substituted oxy;

5. optionally substituted alkoxy;

6. optionally substituted amino;

7. substituted carbonyl;

8. optionally substituted carboxyl;

9. optionally substituted amide;

10. Sulfur at various oxidation levels (II or IV or VI) such as sulphide sulfurants, sulfoxides or optionally substituted sulphones;

12. C ₂ -C 7 linear, branched or cyclic optionally substituted alkenyl;

13. C ₂ -C 6 alkynyl linear or branched optionally substituted;

Aryl or optionally substituted heteroaryl;

15. optionally substituted heterocycloalkyl;

R6 is a heteroaryl (5- or 6-membered with 1 to 4 heteroatom selected from N, S or O) linked to the azacarboline moiety by either a C or an N belonging to R6, R6 being optionally substituted; R6 may also represent C (O) NRIaRIb or an optionally substituted heterocycloalkyl or -C (O) optionally substituted heterocycloalkyl, such that RIa and RIb may be independently of one another:

1. H;

3. C2-C6 linear or branched alkenyl optionally mono or di substituted;

4. C2-C6 linear or branched alkynyl optionally mono or di substituted;

5. aryl optionally mono or di substituted;

6. optionally mono or di substituted heteroaryl;

7. optionally mono or di substituted benzyl;

8. COalkyl optionally mono or di substituted;

9. optionally mono or di substituted Caryl;

10. optionally mono or di substituted heteroaryl;

11. C02alkyl optionally mono or di substituted;

12. C02aryl optionally mono or di substituted;

13. CO2heteroaryl optionally mono or di substituted;

14. CONH2,

15. CONHalkyl optionally mono or di substituted;

16. CONHaryl optionally mono or di substituted;

17. CONHheteroaryl optionally mono or di substituted;

18. CON (alkyl) 2 optionally mono or di substituted;

19. C0N (aryl) 2 optionally mono or di substituted;

Compounds of formula (I) as defined in claim 1 wherein

- R3, R4 can be independently of one another:

1. H;

2 F ;

3. Cl;

4. Br;

5. I;

6. CF ₃ ;

7. OR2a;

8. NRIaRIb;

9. COR2a;

10. CO ₂ R2a;

11. CO (NRIaRIb);

12. SR2a;

13. SOR 2a;

14. SO ₂ R2a;

17. C ₂ -C 6 linear or branched alkynyl optionally mono or di or tri substituted by R2a, R2b, R2c;

19. heterocycloalkyl optionally mono or di or tri substituted by R2a, R2b, R2c;

-RIa and RIb can be independently of each other:

1. H;

2. CpCio linear or branched or cyclic (C3-C7) alkyl optionally mono or di substituted by R2a R2b;

Aryl optionally mono or di substituted with R2a R2b;

6. heteroaryl optionally mono or di substituted with R2a R2b;

Benzyl optionally mono or di substituted with R2a R2b;

8. COalkyl optionally mono or di substituted with R2a R2b;

9. Caryl optionally mono or di substituted with R2a R2b;

10.Heteroaryl optionally mono or di substituted with R2a R2b;

11. Cθ ₂ alkyl optionally mono or di substituted with R2a R2b;

12. Cθ ₂ aryl optionally mono or di substituted with R2a R2b;

13. C _{2 2} heteroaryl optionally mono or di substituted with R2a R2b;

14. CONH ₂ ,

15. CONHalkyl optionally mono or di substituted with R2a R2b;

16. CONHaryl optionally mono or di substituted with R2a R2b;

17. CONHheteroaryl optionally mono or di substituted with R2a R2b;

18. CON (alkyl) ₂ optionally mono or di substituted with R2a R2b;

19. C0N (aryl) ₂ optionally mono or di substituted with R2a R2b;

1. F;

2. Cl;

3. Br;

4. I;

5. CF ₃ ;

C3-C7 cycloalkyl optionally mono or poly substituted with different R3a;

8. C ₂ -C 6 alkenyl optionally mono or poly substituted with different R 3a;

9. C ₂ -C 6 alkynyl optionally mono or poly substituted with different R 3a;

10. OH;

O-cycloalkyl (C3-C7) optionally mono or poly substituted with different R3a;

13. O-aryl optionally mono or poly substituted with different R3a;

Aryl optionally mono or poly substituted with different R3a;

15. heteroaryl optionally mono or poly substituted with different R3a;

16. heterocycloalkyl optionally mono or poly substituted with different R3a;

17. NH ₂ ;

18. NH- (C 1 -C 10 alkyl) or C ₃ -C ₇ cycloalkyl or heterocycloalkyl) each optionally mono or poly group substituted with different R 3a;

19. N (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl) 2 each group being optionally mono or poly substituted with different R 3a;

23. NHC (O) R3a;

24. N (C ₁ -C 10 alkyl) C (O) R 3 a;

25. N (R3a) C (O) R3b;

26. NHS (O ₂ ) R3a;

27. N (C 1 -C 10 alkyl) S (O ₂ ) R 3 a;

28. N (R3a) S (O) ₂ R3b;

29. CO ₂ R3a;

30. SR3a;

31. SOR3a;

32. SO ₂ R3a. where R3a and R3b are selected from:

1. halogen;

2. CF ₃ ;

3. CpCio linear or branched alkyl

4. C ₃ -C ₇ cycloalkyl;

5. C ₂ -C ₆ alkenyl;

6. C ₂ -C ₆ alkynyl;

7. CpCio alkylhydroxy

8. C1-C10 alkoxy

9. CpCio alkylamino

10. OH;

11. linear, branched or cyclic (C ₃ -C ₇ ) -alkyl (C ₁ -C ₁₀ );

12. O-aryl;

13. aryl;

14. heteroaryl;

15. heterocycloalkyl;

16. NH ₂ ;

17. NH (C (C _r Cio) cycloalkyl or (C ₃ -C _7));

18. N (alkyl (C _r Cio) cycloalkyl or (C ₃ -C ₇₎₎ _2;

19. NH- (aryl or heteroaryl);

20. N (aryl or heteroaryl) 2;

21. N (aryl or heteroaryl) (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl);

22. NHC (O) - (C ₁ -C ₁₀ ) alkyl or C ₃ -C ₇ cycloalkyl or heterocycloalkyl;

23. NHC (O) - (aryl or heteroaryl);

24. NHS (O) ₂ - (C ₁ -C ₁₀ alkyl) or (C ₃ -C ₇ ) cycloalkyl or heterocycloalkyl;

25. NHS (O) ₂ - (aryl or heteroaryl);

26. CO (Ci-CiO linear or branched alkyl);

27. CO (Ci-Ci ₀ alkylamino);

28. CO ₂ (Ci-CiO linear or branched alkyl);

29. C (O) NH (Ci-Ci ₀ linear or branched alkyl);

30. C (O) N (Ci-CiO linear or branched alkyl) ₂ ;

31. S (C1-C10 linear or branched alkyl);

32. SO (Ci-Ci ₀ linear or branched alkyl);

33. SO ₂ (Ci-CiO linear or branched alkyl)

Compounds according to claim 1 characterized in that: - R3, R4 can be independently of one another:

1. H;

2 F ;

3. Cl;

4. Br;

5. I;

6. CF ₃ ;

7. OR2a;

8. NRIaRIb;

9. COR2a;

10. CO ₂ R2a;

11. CO (NRIaRIb);

12. SR2a;

13. SOR2a;

14. SO ₂ R2a;

19. heterocycloalkyl optionally mono or di or tri substituted by R2a, R2b, R2c;

- R6 is a heteroaryl (5 or 6-membered with 1 to 4 N, S or O heteroatom) linked to the azacarboline unit or by a C or N belonging to R6, R6 being optionally mono or di or tri substituted by R2a, R2b, R2c; wherein:

-RIa and RIb can be independently of each other: 1. H;

Aryl optionally mono or di substituted with R2a R2b;

6. heteroaryl optionally mono or di substituted with R2a R2b;

Benzyl optionally mono or di substituted with R2a R2b;

8. COalkyl optionally mono or di substituted with R2a R2b;

9. Caryl optionally mono or di substituted with R2a R2b;

10.Heteroaryl optionally mono or di substituted with R2a R2b;

11. Cθ ₂ alkyl optionally mono or di substituted with R2a R2b;

12. Cθ ₂ aryl optionally mono or di substituted with R2a R2b;

13. C _{2 2} heteroaryl optionally mono or di substituted with R2a R2b;

14. CONH ₂ ,

15. CONHalkyl optionally mono or di substituted with R2a R2b;

16. CONHaryl optionally mono or di substituted with R2a R2b;

17. CONHheteroaryl optionally mono or di substituted with R2a R2b;

18. C0N (alkyl) ₂ optionally mono or di substituted with R2a R2b;

19. C0N (aryl) ₂ optionally mono or di substituted with R2a R2b;

1. F;

2. Cl;

3. Br;

4. I;

5. CF ₃ ;

C3-C7 cycloalkyl optionally mono or poly substituted with different R3a;

8. C ₂ -C 6 alkenyl optionally mono or poly substituted with different R 3a;

9. C ₂ -C 6 alkynyl optionally mono or poly substituted with different R 3a;

10. OH;

O-cycloalkyl (C3-C7) optionally mono or poly substituted with different R3a;

13. O-aryl optionally mono or poly substituted with different R3a;

Aryl optionally mono or poly substituted with different R3a;

15. heteroaryl optionally mono or poly substituted with different R3a;

16. heterocycloalkyl optionally mono or poly substituted with different R3a;

17. NH ₂ ;

19. N (C 1 -C 10 alkyl) or C ₃ -C ₇ cycloalkyl) 2 each group being optionally mono or poly substituted with different R 3a;

23. NHC (O) R3a;

24. N (C ₁ -C 10 alkyl) C (O) R 3 a;

25. NHC (O) - (C 1 -C 10 alkyl) or C ₃ -C ₇ cycloalkyl or heterocycloalkyl each group being optionally mono or poly substituted with different R 3a;

26. NC (O) (C 1 -C 10 alkyl) or C ₃ -C ₇ cycloalkyl or heterocycloalkyl each group being optionally mono or poly substituted with different R 3a;

30. NHS (O ₂ ) R3a;

31. N (C 1 -C 10 alkyl) S (O ₂ ) R 3 a;

34. NHS (O ₂ ) - (aryl or heteroaryl) optionally mono or poly substituted with different R3a;

35. NS (O ₂ ) (aryl or heteroaryl) ₂ each group being optionally mono or poly substituted with different R3a;

36. NS (O ₂ ) (aryl or heteroaryl) (C 1 -C 10 alkyl) or C ₃ -C ₇ cycloalkyl or heterocycloalkyl) each group being optionally mono or poly substituted with different R 3a; COR3a;

37. CO ₂ R3a;

38. SR3a;

39. SOR3a;

40. SO ₂ R3a. in which R3a is selected from:

1. halogen;

2. CF ₃ ;

3. CpCio linear or branched alkyl

4. C ₃ -C ₇ cycloalkyl;

5. C ₂ -CO alkenyl;

6. C ₂ -C ₆ alkynyl;

7. OH;

8. linear, branched or cyclic (C ₃ -C ₇ ) -alkyl (C ₁ -C ₁₀ );

9. O-aryl;

10. aryl;

11. heteroaryl;

12. heterocycloalkyl;

13. NH ₂ ;

14. NH (C (C _r Cio) cycloalkyl or (C ₃ -C _7));

15. N (alkyl (C _r Cio) cycloalkyl or (C ₃ -C ₇₎₎ _2;

16. NH- (aryl or heteroaryl);

17. N (aryl or heteroaryl) ₂ ;

18. N (aryl or heteroaryl) (C ₁ -C ₁₀ alkyl) or C ₃ -C ₇ cycloalkyl);

21. NHC (O) - (aryl or heteroaryl);

22. NC (O) (aryl or heteroaryl) ₂ ;

26. NHS (O ₂ ) - (aryl or heteroaryl);

27. NS (O ₂ ) (aryl or heteroaryl) ₂ ;

29. CO (Ci-Ci ₀ linear or branched alkyl);

30. CO ₂ (Ci-CiO linear or branched alkyl);

31. C (O) NH (Ci-Ci ₀ linear or branched alkyl);

32. C (O) N (Ci-Ci ₀ linear or branched alkyl) _2;

33. S (Ci-CiO linear or branched alkyl);

34. SO (Ci-CiO linear or branched alkyl);

35. Sθ2 (Ci-Cio linear or branched alkyl).

Compounds according to claim 1, selected from:

4-cyclopropyl-3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

4-methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

Ethyl 6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine-3-carboxylate;

6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-4-methyl-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

4-chloro-3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-chloro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-bromo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; - (2E) -3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] prop-2-enoate ethyl;

3-fluoro-4- [3- (morpholin-4-yl) phenyl] -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine-3-carboxylic acid;

[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] methanol;

4- {methyl [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] amino} -1- (pyrrolidin-1-yl) ) butan-1-one;

6- (furan-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

6- (5-fluoropyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

2- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] propan-2-ol;

6- (6-fluoropyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; N, N-diethyl-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-amine;

3- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-b '] dipyridine;

3-methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-c: 5,4-c] dipyridine;

3-fluoro-6- (5-methoxypyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- (4-methoxypyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

6- (1-Benzyl-1H-pyrazol-4-yl) -3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 3-fluoro-6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- [5- (methylsulfanyl) pyridin-3-yl] -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] -2-methylbut-3-yn- 2-ol;

4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] -2-methylbut-3-yn- 2-amme; N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] -2-methylbut-3 -yn-2-yl} methanesulfonamide;

3-fluoro-4- [3-methyl-3- (piperazin-1-yl) but-1-yn-1-yl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-di] b: 5.4- [c] dipyridine; 4- [3-Methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] -2-methylbut-3-yn- 2-ol;

4- [3-Methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] -2-methylbut-3-yn- 2-amine; N- {4- [3-methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] -2-methylbut-3 -yn-2-ylmmethanesulfonamide;

3-fluoro-4- [4- (morpholin-4-yl) piperidin-1-yl] -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] ] dipyridine;

3-fluoro-4- (6-methoxypyridin-3-yl) -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; N- {3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} methanesulfonamide;

3-fluoro-4- (5-methylfuran-2-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 3-fluoro-4- (1-methyl-1H-indol-5-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

4 - ({3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] phenyl} ammo) acid) -4-oxobutanoic acid;

3-fluoro-6- (5-methoxypyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- (4-methoxypyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-4- [4- (propan-2-yl) piperazin-1-yl] -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] ] dipyridine; 3-fluoro-4- (piperidin-1-yl) -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] -N, N-dimethylaniline; 3-fluoro-4- (1-methyl-1H-indol-5-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-4- (1-methyl-1H-pyrazol-4-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] benzyl} acetamide;

3-fluoro-4,6-di (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; N- {2- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenyl} methanesulfonamide;

3-fluoro-4- (1H-pyrazol-4-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 3-fluoro-4- [3- (methylsulfonyl) phenyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- (piperazin-1-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-amine;

3-Fluoro-4- {4- [3- (morpholin-4-yl) propyl] piperazin-1-yl} -6- (pyrid-3-yl) -9H-pyrrolo [2,3-b] 4- [4-] dipyridine;

3- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] piperazin-1-yl} N, N-dipropylpropan-1-amine;

3-ethoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N, N-diethyl-3- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] piperazin-1-yl} propan-1-amine; N, N-diethyl-2- {4- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] -1H-pyrazol 1-yethanamine;

3-fluoro-4-methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridine-6-carbonitrile;

3- (2-methoxyethoxy) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-methoxy-6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N, N-diethyl-2- [4- (3-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) -3,5-dimethyl-1H-pyrazol 1-yl] ethanamine;

N- [2- (dimethylamino) ethyl] -2- [4- (3-methoxy-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) -1H-pyrazol 1-acetamide;

3- (1H-pyrazol-4-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

9H-pyrrolo [2,3-b: 5,4-c] dipyridine-6-carboxylic acid;

N- [3- (dimethylamino) propyl] -N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridm] [Phenyl] methanesulfonamide; (4-methylpiperazin-1-yl) (9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) methanone;

3-fluoro-6- (thiophen-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N, N-diethyl-2- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] phenoxy} ethanamine;

N- [2- (dimethylamino) ethyl] -5- [3-fluoro-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4- yl] pyridine-2-carboxamide;

4- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] phenol;

3-fluoro-6- (isoquinolin-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; N, N-dimethyl-3- {4- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] phenoxy} propanediol the mine;

N, N, 4-Triethyl-5- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] pyrid-2-amine ;

4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] -N- (prop-2-en) -l-yl) anilme;

N- (2-methylpropan-2-yl) -5- (9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) pyridin-3-carboxamide;

5- (3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) -N- (2-methylpropan-2-yl) pyrid-3-carboxamide;

3-fluoro-6- (1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

6-chloro-3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- {4- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-yl] phenoxy} propan-1-amine;

6- (1-methyl-1H-pyrazol-4-yl) -3- {4- [3- (morpholin-4-yl) propoxy] phenyl} -9H-pyrrolo [2,3-b: 5.4 dipyridine; N, N-diethyl-N-Cό-Cl-methyl-1H-pyrazol-4H-pyrrolo [4-yl] -3'-dipyridyl-5-yl] phenoxy} ethanamine;

4- [3- (4-ethylpiperazin-1-yl) -3-methylbut-1-yn-1-yl] -3-fluoro-6- (1-methyl-1H-pyrazol-4-yl) - 9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N- [3- (dimethylamino) propyl] -N- {4- [3- (2-methoxyethoxy) -6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3- b: 5,4-c '] dipyridin-4-yl] phenyl} methanesulfonamide;

N-ethyl-3- {4- [3- (2-methoxyethoxy) -6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c]; '] dipyridin-4-yl] phenoxy} propan-1-amine;

4 - ({[3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridin-4-yl] oxy} methyl) -N, N-dimethylaniline; 3-Fluoro-6- (pyrid-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl [4- (dimethylamino) phenyl] carbamate;

3-fluoro-6- (1-methyl-1H-imidazol-5-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N- {4- [2- (dimethylamino) ethoxy] benzyl} -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-amine;

6- (pyridin-3-yl) -N - {[2- (pyridin-4-yl) cyclopropyl] methyl} -9H-pyrrolo [2,3-b: 5,4-c '] dipyridm-3- amine;

N- (4-methyl-4-nitropentyl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-amine;

piperazin-1-yl [4 - ({[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-yl] amino} methyl) phenyl ] methanone; N- [4- (aminomethyl) benzyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-amine;

6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine-3-carbonitrile;

6- (3,5-dimethyl-1H-pyrazol-4-yl) -3- (pyridin-3-yl) -9H-beta-carboline;

2- {3- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] phenoxy} ethanamine;

3- (4 - {[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] oxy} phenyl) propan-1-ol ;

N, N-diethyl-3- (4 - {[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] oxy} phenyl ) propan-1-amino; N, N-diethyl-2 - {[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-yl] oxy} ethanol;

Compounds according to claim 1, selected from:

4-cyclopropyl-3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

4-methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] phenol;

3-fluoro-4-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] butane-1,2-diol;

[3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] (phenyl) methanone;

3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] benzenesulfonamide;

2-methylpropyl 6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c '] dipyridine-3-carboxylate; N-methyl-N-propyl-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-amine;

Ethyl 6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine-3-carboxylate;

6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-4-methyl-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

4-chloro-3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-chloro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine-3-carboxylic acid;

[6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] methanol;

6- (furan-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

6- (5-fluoropyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

2- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] propan-2-ol;

3- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-b '] dipyridine;

3-methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-c: 5,4-c] dipyridine;

3-fluoro-6- (5-methoxypyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- (4-methoxypyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-4- (4-methylthiophen-3-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 3- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] -N, N-dimethylaniline;

2- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-4-yl] benzonitrile.

3-fluoro-6- (5-methoxypyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- (4-methoxypyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- [5- (methylsulfanyl) pyridin-3-yl] -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 3-Fluoro-6- {1- [2- (morpholin-4-yl) ethyl] -1H-pyrazol-4-yl} -9H-pyrrolo [2,3-b: 5,4-c] dipyridine ; 3-fluoro-4- [4- (propan-2-yl) piperazin-1-yl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] ] dipyridme;

3-fluoro-4- (1H-pyrazol-4-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- (piperazin-1-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-amine;

3-ethoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-iodo-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- (1-methyl-1H-pyrazol-3-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; N, N-diethyl-3- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-4-yl] piperazin-1-yl} propan-1-amine;

3-fluoro-4-methoxy-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- [4- (morpholin-4-yl) phenyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N-propyl-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-amine;

3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridine-6-carbonitrile;

3- (2-methoxyethoxy) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N, N-diethyl-3- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyrid-3-yl] benzamide;

3- (3,5-dimethyl-1H-pyrazol-4-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-methoxy-6- (1-methyl-1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3- (1H-pyrazol-4-yl) -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

9H-pyrrolo [2,3-b: 5,4-c] dipyridine-6-carboxylic acid; N- [3- (dimethylamino) propyl] -N- {4- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridm] [Phenyl] methanesulfonamide;

(4-methylpiperazin-1-yl) (9H-pyrrolo [2,3-b: 5,4-c] dipyridin-6-yl) methanone;

3-fluoro-6- (thiophen-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

N- [2- (dimethylamino) ethyl] -5- [3-fluoro-6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridm-4- yl] pyridine-2-carboxamide;

4- [6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridin-3-yl] phenol;

3- [4- (piperazin-1-yl) phenyl] -6- (pyridin-3-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine; 3-fluoro-6- (isoquinolin-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

3-fluoro-6- (1H-pyrazol-4-yl) -9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

6-chloro-3-fluoro-9H-pyrrolo [2,3-b: 5,4-c] dipyridine;

6. Medicament, characterized in that it comprises a compound of formula (I) according to any one of claims 1 to 5, or a salt of addition of this compound to a pharmaceutically acceptable acid.

7. Pharmaceutical compositions containing, as active ingredient, a compound according to any one of the preceding claims as well as at least one pharmaceutically compatible excipient. Pharmaceutical compositions according to the preceding claim used for the treatment of cancer.

9 Use of a compound of formula (I) according to any one of claims 1 to 5 for the preparation of a medicament for the treatment of diseases sensitive to deregulation of PIM kinases.

10. Use of a compound of formula (I) according to any one of claims 1 to 5 for the preparation of a medicament for the treatment of cancer

11 - Use of the products of formula (I) as defined in claims 1 to 5 for the preparation of medicaments for the chemotherapy of cancers.

Compounds of formula (I) as defined in any one of claims 1 to 5 as kinase inhibitors.

Compounds of formula (I) as defined in any one of claims 1 to 5 as inhibitors of PIM kinases.

14. Process for the synthesis of the compounds of formula (I) as defined in any one of claims 1 to 5 described in scheme 1 below:

Wherein the substituents R3, R4 have the meanings given above or hereafter, and R represents either the values of R6 as defined above or the following values: OH, OCH ₃ , OS (O) ₂ CF ₃ , Cl, SCH ₃ , CN.

As new industrial products, synthetic intermediates D3:

in which the substituents R3, R4 have the meanings indicated in any one of claims 1 to 5, and R represents the values of R6 as defined in any one of claims 1 to 5 and the following values: OH, OCH ₃ , OS (O) ₂ CF ₃ , Cl, SCH ₃ , CN.

16 As new industrial products, synthetic intermediates D3:

in which the substituent R3 represents a fluorine atom or a methoxy radical, and the substituent R4 represents a hydrogen atom, R being chosen from the values of R6 as defined in any one of claims 1 to 5 and the values OH, OCH ₃ , OS (O) ₂ CF ₃ , Cl, SCH ₃ ,

CN.

17 As new industrial products, synthetic intermediates D4:

wherein the substituents R 3 and R 4 have the meanings indicated in any one of claims 1 to 5 and R represents the following values: OH, OCH ₃ , OS (O) ₂ CF ₃ , Cl, SCH ₃ , CN.