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HRP20190805T1 - Spojevi triazolopirimidina i njihova uporaba - Google Patents

Spojevi triazolopirimidina i njihova uporaba Download PDF

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HRP20190805T1
HRP20190805T1 HRP20190805TT HRP20190805T HRP20190805T1 HR P20190805 T1 HRP20190805 T1 HR P20190805T1 HR P20190805T T HRP20190805T T HR P20190805TT HR P20190805 T HRP20190805 T HR P20190805T HR P20190805 T1 HRP20190805 T1 HR P20190805T1
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alkyl
independently selected
compound
pharmaceutically acceptable
acceptable salt
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HRP20190805TT
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Ho Man Chan
Xiang-Ju Justin Gu
Ying Huang
Ling Li
Yuan Mi
Wei Qi
Martin Sendzik
Yongfeng SUN
Long Wang
Zhengtian Yu
Hailong Zhang
Ji Yue Zhang (Jeff)
Man ZHANG
Qiong Zhang
Kehao Zhao
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Novartis Ag
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Claims (27)

1. Spoj, naznačen time, što je predstavljen Formulom (I): ili njegova farmaceutski prihvatljiva sol, u kojoj: je jednostruka veza ili dvostruka veza; R1 i R2 su neovisno H ili halogen; R3 je neovisno odabran od: halogena, fenila i 5-članog do 6-članog heteroarila koji obuhvaća ugljikove atome i 1-4 heteroatoma koji su odabrani od N, NRa, O i S(O)p; pri čemu su navedeni fenil i heteroaril supstituirani s 0-3 R3A; svaki R3A je neovisno odabran od: halogena, CN, -(O)m-(C1-C6 alkila supstituiranog s 0-1 R3B), C1-C6 haloalkila, C1-C6 haloalkoksi, R3C, -OR3C, -C(=O)R3D, NR3ER3F, -C(=O)NR3ER3F, -NHC(=O)R3D, -S(=O)2R3D, -S(=O)2NR3ER3F, -NHS(=O)2(C1-C4 alkil) i -CR3CR3ER3G; R3B je neovisno odabran od: OH, NReRf, C1-C4 alkoksi, -C(=O)NReRf, -S(=O)2(C1-C4 alkil), -NHC(=O)(C1-C4 alkil), i 5-članog do 6-članog heterocikloalkila koji obuhvaća ugljikove atome i 1-2 heteroatoma koji su odabrani od N, NRa, O, i S(O)p; pri čemu je navedeni heterocikloalkil supstituiran s 0-2 RC; svaki R3C je neovisno odabran od: C3-C6 cikloalkila, fenila, i 4-članog do 7-članog heterocikla koji obuhvaća ugljikove atome i 1-4 heteroatoma koji su odabrani od N, NRa, O, i S(O)p; pri čemu je svaki dio skupine supstituiran s 0-2 Rc; svaki R3D je neovisno odabran od: C1-C4 alkil i R3C; R3E i R3G su, pri svakoj pojavi, neovisno odabrani od: H i C1-C4 alkila; svaki R3F je neovisno odabran od: H i C1-C4 alkila supstituiranog s 0-1 Rd; R4 je neovisno odabran od: H, halogena i C1-C4 alkila; R5 je neovisno odabran od OH i C1-C4 alkila; svaki Ra je neovisno odabran od: H, →O, C1-C4 alkila supstituiranog s 0-1 Rb, -C(=O)H, -C(=O)(C1-C4 alkila), -CO2(C1-C4 alkila), C3-C6 cikloalkila, i benzila; Rb je neovisno odabran od: halogena, OH i C1-C4 alkoksi; [0001] svaki Rc je neovisno odabran od: =O, halogena, OH, C1-C4 alkila, C1-C4 haloalkila, C1-C4 alkoksi, i C1-C4 haloalkoksi; Rd je neovisno odabran od: OH i NReRf; Re i Rf su, pri svakoj pojavi, neovisno odabrani od: H i C1-C4 alkila; svaki p je neovisno odabran od 0, 1 i 2; i m i n su, pri svakoj pojavi, neovisno odabrani od 0 i 1.
2. Spoj ili njegova farmaceutski prihvatljiva sol, prema zahtjevu 1, naznačen time, što: [0002] svaki R3A je neovisno odabran od: halogena, CN, -(O)m-(C1-C4 alkila supstituiranog s 0-1 R3B), C1-C4 haloalkila, C1-C4 haloalkoksi, R3C, -C(=O)R3D, NR3ER3F, [0003] -C(=O)NR3ER3F, -S(=O)2R3D, -S(=O)2NHR3F, -NHS(=O)2(C1-C4 alkil), [0004] -O-C3-C6 cikloalkila, i [0005] ; Ra je neovisno odabran od: H, →O, C1-C4 alkila supstituiranog s 0-1 Rb, -C(=O)H, -C(=O)(C1-C4 alkila), -CO2(C1-C4 alkila), i C3-C6 cikloalkila; R4 je H; m je neovisno odabran od 0 i 1; i n je 0.
3. Spoj ili njegova farmaceutski prihvatljiva sol, prema zahtjevu 1 ili zahtjevu 2, naznačen time, što: R1 je neovisno H ili F; R2 je H; i R3 je neovisno odabran od: fenila, i 6-članog heteroarila koji obuhvaća ugljikove atome i 1-2 heteroatoma koji su odabrani od N i NRa; pri čemu su navedeni fenil i heteroaril supstituirani s 0-3 R3A.
4. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 3, naznačen time, što: R3 je neovisno odabran od: fenila, piridila, pirimidila, piridazinila i pirazinila; pri čemu je svaki dio skupine supstituiran s 0-3 R3A.
5. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 4, naznačen time, što: R3 je neovisno odabran od: i .
6. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 4, naznačen time, što: R3 je neovisno odabran od: i [0006] ; svaki R3A je neovisno odabran od: halogena, CN, -(O)m-(C1-C4 alkila supstituiranog s 0-1 R3B), C1-C4 haloalkila, C1-C4 haloalkoksi, -C(=O)NH2, -C(=O)NH(C1-C4 alkila), -C(=O)N(C1-C4alkila)2, -C(=O)N(C1-C4alkil)(CH2)2N(C1-C4 alkila)2, -CH2NHC(=O)(C1-C4 alkila), -S(=O)2R3D, -S(=O)2NH(C1-C4 alkila supstituiranog s 0-1 OH), -NHS(=O)2(C1-C4 alkila), NH2, -NH(C1-C4 alkila), -N(C1-C4 alkila)2, C3-C6 cikloalkila,
i [0007] ; R3B je neovisno odabran od: OH, NH2, NH(C1-C4 alkila), N(C1-C4 alkila)2, C1-C4 alkoksi, -C(=O)N(C1-C4 alkila)2, -S(=O)2(C1-C4 alkila),
i ; R3D je neovisno odabran od: C1-C4 alkila i 1H-piperidin-4-ila; i svaki Ra je neovisno odabran od: H, C1-C4 alkila, -C(=O)H, -C(=O)(C1-C4 alkila), i -CO2(C1-C4 alkila).
7. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 6, naznačen time, što: R3 je neovisno odabran od: i ; svaki R3A je neovisno odabran od: halogena, CN, -(O)m-(C1-C4 alkila supstituiranog s 0-1 R3B), C1-C4 haloalkila, C1-C4 haloalkoksi, -C(=O)NH2, -C(=O)NH(C1-C4 alkila), -C(=O)N(C1-C4alkila)2, -C(=O)N(C1-C4 alkil)(CH2)2N(C1-C4 alkila)2, -CH2NHC(=O)(C1-C4alkila), -S(=O)2(C1-C4alkila), NH2, NH(C1-C4 alkila), N(C1-C4 alkila)2, C3-C6 cikloalkila,
i ; [0008] R3B je neovisno odabran od: OH, N(C1-C4 alkila)2, C1-C4 alkoksi, [0009] -C(=O)N(C1-C4 alkila)2, -S(=O)2(C1-C4 alkila),
i ; i svaki Ra je neovisno odabran od: H, C1-C4 alkila, -C(=O)H, -C(=O)(C1-C4 alkila), i -CO2(C1-C4 alkila).
8. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 7, naznačen time, što: svaki R3A je neovisno odabran od: F, Cl, CH3, -CH2OH, CH2F, CHF2, CF3, CN, -OCH3, -OCH2CH3, -OCH(CH3)2, -OCHF2, -C(=O)N(CH3)2, -CH2NHC(=O)CH3, -S(=O)2CH3, NH2, ciklopropila, i [0010] .
9. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 8, naznačen time, što je navedeni spoj predstavljen Formulom (IA-1): ili njegova farmaceutski prihvatljiva sol, gdje: R1 je neovisno H ili F; i R3A je neovisno odabran od: F, CH3, -CH2OH, CH2F, CHF2, CF3, i -OCH3.
10. Spoj prema zahtjevu 1 ili zahtjevu 2, naznačen time, što: R1 je neovisno H ili F; R2 je H; R3 je neovisno 5-člani heteroaril koji obuhvaća ugljikove atome i 1-4 heteroatoma koji su odabrani od N, NRa, O, i S(O)p; pri čemu je navedeni heteroaril supstituiran s 0-3 R3A; i Ra je neovisno odabran od: H, C1-C4 alkila supstituiranog s 0-1 Rb, -C(=O)H, -C(=O)(C1-C4 alkila), -CO2(C1-C4 alkila), C3-C6 cikloalkila, i benzila.
11. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1, 2 ili 10, naznačen time, što: R3 je neovisno odabran od: , , , , i .
12. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 11, naznačen time, što: R1 je F.
13. Spoj ili njegova farmaceutski prihvatljiva sol, prema zahtjevu 1, naznačen time, što je navedeni spoj odabran iz niza koji čine:
14. Spoj prema zahtjevu 1, naznačen time, što navedeni spoj je: [0011] , ili njegova farmaceutski prihvatljiva sol.
15. Spoj prema zahtjevu 1, naznačen time, što navedeni spoj je: [0012] , ili njegova farmaceutski prihvatljiva sol.
16. Spoj prema zahtjevu 1, naznačen time, što navedeni spoj je: [0013] , ili njegova farmaceutski prihvatljiva sol.
17. Spoj prema zahtjevu 1, naznačen time, što navedeni spoj je: [0014] , ili njegova farmaceutski prihvatljiva sol.
18. Spoj prema zahtjevu 1, naznačen time, što navedeni spoj je: [0015] , ili njegova farmaceutski prihvatljiva sol.
19. Spoj prema zahtjevu 1, naznačen time, što navedeni spoj je: [0016] , ili njegova farmaceutski prihvatljiva sol.
20. Farmaceutski pripravak, naznačen time, što obuhvaća jedan ili više farmaceutski prihvatljivih nosača i spoj ili njegovu farmaceutski prihvatljivu sol, prema bilo kojem od zahtjeva 1 do 19.
21. Farmaceutski pripravak prema zahtjevu 20, naznačen time, što nadalje obuhvaća najmanje jedno dodatno terapijsko sredstvo.
22. Farmaceutski pripravak prema zahtjevu 21, naznačen time, što je navedeno dodatno terapijsko sredstvo odabrano od drugih antikancerogenih sredstava, imunomodulatora, antialergijskih sredstava, antiemetika, sredstava za ublažavanje boli, citozaštitnih sredstava, i njihovih kombinacija.
23. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 19, naznačen time, što je za uporabu u terapiji.
24. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 19, za uporabu kao što je navedeno u patentnom zahtjevu 23, naznačen time, što je navedena terapija liječenje bolesti ili poremećaja posredovanog s EED i/ili PRC2.
25. Spoj ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 19, za uporabu kao što je navedeno u patentnom zahtjevu 24, naznačen time, što je navedena bolest odabrana ili je poremećaj odabran od difuznog limfoma velikih B-stanica, folikularnog limfoma, drugih limfoma, leukemije, multiplog mijeloma, mezotelioma, raka želuca, malignog rabdoidnog tumora, hepatocelularnog karcinoma, raka prostate, karcinoma dojke, karcinoma žučnih puteva i žučnog mjehura, karcinoma mjehura, tumora mozga uključujući neuroblastom, schwannom, gliom, glioblastom i astrocitom, raka grlića maternice, raka debelog crijeva, melanoma, raka endometrija, raka jednjaka, raka glave i vrata, raka pluća, nazofaringealnog karcinoma, raka jajnika, raka gušterače, karcinoma bubrežnih stanica, rektalnog raka, karcinoma štitnjače, paratiroidnih tumora, tumora maternice, sarkoma mekog tkiva.
26. Kombinacija, naznačena time, što se tvori od spoja ili njegove farmaceutski prihvatljive soli, prema bilo kojem od zahtjeva 1 do 19, i najmanje jednog dodatnog terapijskog sredstva.
27. Kombinacija prema zahtjevu 26, naznačena time, što je dodatno terapijsko sredstvo odabrano od drugih antikancerogenih sredstava, imunomodulatora, antialergijskih sredstava, antiemetika, sredstava za ublažavanje boli, citozaštitnih sredstava, i njihovih kombinacija.
HRP20190805TT 2014-12-23 2019-04-29 Spojevi triazolopirimidina i njihova uporaba HRP20190805T1 (hr)

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Application Number Priority Date Filing Date Title
CN2014094644 2014-12-23
CN2015095320 2015-11-23
PCT/IB2015/059843 WO2016103155A1 (en) 2014-12-23 2015-12-21 Triazolopyrimidine compounds and uses thereof
EP15820637.5A EP3237418B1 (en) 2014-12-23 2015-12-21 Triazolopyrimidine compounds and uses thereof

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IL263429B (en) * 2016-06-20 2022-08-01 Novartis Ag Crystalline forms of a triazolopyrimidine compound
EP3472161B1 (en) * 2016-06-20 2020-03-25 Novartis AG Triazolopyridine compounds and uses thereof
CN109790166A (zh) * 2016-06-20 2019-05-21 诺华股份有限公司 咪唑并吡啶化合物用于治疗癌症
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