UA73073C2 - Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція - Google Patents
Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція Download PDFInfo
- Publication number
- UA73073C2 UA73073C2 UA99116029A UA99116029A UA73073C2 UA 73073 C2 UA73073 C2 UA 73073C2 UA 99116029 A UA99116029 A UA 99116029A UA 99116029 A UA99116029 A UA 99116029A UA 73073 C2 UA73073 C2 UA 73073C2
- Authority
- UA
- Ukraine
- Prior art keywords
- amino
- carbon atoms
- cyano
- quinolinecarbonitrile
- carbonitrile
- Prior art date
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- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 title 1
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 407
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 225
- 150000001875 compounds Chemical class 0.000 claims abstract description 191
- -1 halogenmethyl Chemical group 0.000 claims abstract description 121
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 116
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 50
- 239000001257 hydrogen Substances 0.000 claims abstract description 50
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 35
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 34
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 27
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 27
- 150000002367 halogens Chemical class 0.000 claims abstract description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 26
- QZZYYBQGTSGDPP-UHFFFAOYSA-N quinoline-3-carbonitrile Chemical class C1=CC=CC2=CC(C#N)=CN=C21 QZZYYBQGTSGDPP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 22
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 17
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 15
- 125000004849 alkoxymethyl group Chemical group 0.000 claims abstract description 14
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 11
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims abstract description 10
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims abstract description 7
- 125000004438 haloalkoxy group Chemical group 0.000 claims abstract 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 191
- 239000002904 solvent Substances 0.000 claims description 137
- 206010028980 Neoplasm Diseases 0.000 claims description 56
- 238000006243 chemical reaction Methods 0.000 claims description 49
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
- 125000001424 substituent group Chemical group 0.000 claims description 34
- 238000000034 method Methods 0.000 claims description 33
- 230000005764 inhibitory process Effects 0.000 claims description 29
- 238000010438 heat treatment Methods 0.000 claims description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 27
- 239000012442 inert solvent Substances 0.000 claims description 26
- 229910052799 carbon Inorganic materials 0.000 claims description 25
- 125000004970 halomethyl group Chemical group 0.000 claims description 21
- 150000003254 radicals Chemical class 0.000 claims description 21
- 230000012010 growth Effects 0.000 claims description 20
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 claims description 20
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 19
- 125000003342 alkenyl group Chemical group 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 18
- 239000012634 fragment Substances 0.000 claims description 18
- 102000043136 MAP kinase family Human genes 0.000 claims description 16
- 108091054455 MAP kinase family Proteins 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 16
- 239000003054 catalyst Substances 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 16
- 150000008064 anhydrides Chemical class 0.000 claims description 13
- 238000009835 boiling Methods 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 241000124008 Mammalia Species 0.000 claims description 12
- 239000003153 chemical reaction reagent Substances 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 230000003993 interaction Effects 0.000 claims description 9
- ITGIYLMMAABTHC-ONEGZZNKSA-N (e)-4-(dimethylazaniumyl)but-2-enoate Chemical compound CN(C)C\C=C\C(O)=O ITGIYLMMAABTHC-ONEGZZNKSA-N 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 8
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 8
- TYPPJPWWUXMGRI-UHFFFAOYSA-N 4-(diethylamino)but-2-enoic acid Chemical compound CCN(CC)CC=CC(O)=O TYPPJPWWUXMGRI-UHFFFAOYSA-N 0.000 claims description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 239000002585 base Substances 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 239000003638 chemical reducing agent Substances 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 208000030761 polycystic kidney disease Diseases 0.000 claims description 6
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- DOTGZROJTAUYFQ-OWOJBTEDSA-N (e)-4-bromobut-2-enoic acid Chemical compound OC(=O)\C=C\CBr DOTGZROJTAUYFQ-OWOJBTEDSA-N 0.000 claims description 5
- 230000029936 alkylation Effects 0.000 claims description 5
- 238000005804 alkylation reaction Methods 0.000 claims description 5
- 229910021529 ammonia Inorganic materials 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 claims description 4
- 150000001350 alkyl halides Chemical class 0.000 claims description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 4
- 239000012649 demethylating agent Substances 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- OZMHIFNNCZPJFS-UHFFFAOYSA-N quinoline-7-carbonitrile Chemical compound C1=CC=NC2=CC(C#N)=CC=C21 OZMHIFNNCZPJFS-UHFFFAOYSA-N 0.000 claims description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 4
- ZOJKRWXDNYZASL-NSCUHMNNSA-N (e)-4-methoxybut-2-enoic acid Chemical compound COC\C=C\C(O)=O ZOJKRWXDNYZASL-NSCUHMNNSA-N 0.000 claims description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 3
- JPDTVCOEUUQNSS-UHFFFAOYSA-N 4-(3-bromophenoxy)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1OC1=CC=CC(Br)=C1 JPDTVCOEUUQNSS-UHFFFAOYSA-N 0.000 claims description 3
- WEOXCMIQDJTOOP-UHFFFAOYSA-N 6,7-dimethoxy-4-(3-nitroanilino)quinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC1=CC=CC([N+]([O-])=O)=C1 WEOXCMIQDJTOOP-UHFFFAOYSA-N 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 102000001253 Protein Kinase Human genes 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 150000001448 anilines Chemical class 0.000 claims description 3
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 210000001072 colon Anatomy 0.000 claims description 3
- 238000006073 displacement reaction Methods 0.000 claims description 3
- 239000003937 drug carrier Chemical group 0.000 claims description 3
- 230000008029 eradication Effects 0.000 claims description 3
- 210000003238 esophagus Anatomy 0.000 claims description 3
- 210000003734 kidney Anatomy 0.000 claims description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
- 210000000214 mouth Anatomy 0.000 claims description 3
- 150000007530 organic bases Chemical class 0.000 claims description 3
- 210000001672 ovary Anatomy 0.000 claims description 3
- 210000003800 pharynx Anatomy 0.000 claims description 3
- 108060006633 protein kinase Proteins 0.000 claims description 3
- 210000002784 stomach Anatomy 0.000 claims description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 3
- 210000003932 urinary bladder Anatomy 0.000 claims description 3
- DPAMNPPLTWUUOW-UHFFFAOYSA-N 4-(3-hydroxy-4-methylanilino)-6-methoxy-7-(2-morpholin-4-ylethoxy)quinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C=C(OCCN3CCOCC3)C(OC)=CC2=C1NC1=CC=C(C)C(O)=C1 DPAMNPPLTWUUOW-UHFFFAOYSA-N 0.000 claims description 2
- ISCIEBIOIJWXOX-UHFFFAOYSA-N 4-(4-chloro-2-fluoro-5-hydroxyanilino)-7-[2-(dimethylamino)ethoxy]-6-methoxyquinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C=C(OCCN(C)C)C(OC)=CC2=C1NC1=CC(O)=C(Cl)C=C1F ISCIEBIOIJWXOX-UHFFFAOYSA-N 0.000 claims description 2
- WUTUYQSMZJUIDT-UHFFFAOYSA-N 4-(4-chloro-2-fluoro-5-hydroxyanilino)-7-[3-(dimethylamino)propoxy]-6-methoxyquinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C=C(OCCCN(C)C)C(OC)=CC2=C1NC1=CC(O)=C(Cl)C=C1F WUTUYQSMZJUIDT-UHFFFAOYSA-N 0.000 claims description 2
- REBRBTLJKXGAAU-UHFFFAOYSA-N 4-(cyclohexylamino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC1CCCCC1 REBRBTLJKXGAAU-UHFFFAOYSA-N 0.000 claims description 2
- ZXRTVLOBTDWRJL-UHFFFAOYSA-N 4-[(3,4-dimethoxyphenyl)methylamino]-6,7-diethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OCC)C(OCC)=CC2=NC=C(C#N)C=1NCC1=CC=C(OC)C(OC)=C1 ZXRTVLOBTDWRJL-UHFFFAOYSA-N 0.000 claims description 2
- MOMWLTJRHZNPRC-UHFFFAOYSA-N 4-[(3-bromophenyl)methylamino]-6,7-diethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OCC)C(OCC)=CC2=NC=C(C#N)C=1NCC1=CC=CC(Br)=C1 MOMWLTJRHZNPRC-UHFFFAOYSA-N 0.000 claims description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 2
- 150000001299 aldehydes Chemical class 0.000 claims description 2
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
- 230000033228 biological regulation Effects 0.000 claims description 2
- 210000000481 breast Anatomy 0.000 claims description 2
- 125000002843 carboxylic acid group Chemical group 0.000 claims description 2
- UMAUXDSUHUAKMF-UHFFFAOYSA-N chembl111586 Chemical compound C=12C=C(O)C(O)=CC2=NC=C(C#N)C=1NC1=CC=CC(Br)=C1 UMAUXDSUHUAKMF-UHFFFAOYSA-N 0.000 claims description 2
- 239000012320 chlorinating reagent Substances 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 239000012024 dehydrating agents Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 150000003141 primary amines Chemical class 0.000 claims description 2
- 150000003335 secondary amines Chemical class 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 238000001149 thermolysis Methods 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 5
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 claims 5
- LQFDQJDIWFMWHN-UHFFFAOYSA-N 4-morpholin-4-ylbut-2-enoic acid Chemical compound OC(=O)C=CCN1CCOCC1 LQFDQJDIWFMWHN-UHFFFAOYSA-N 0.000 claims 4
- XFOAIBYWZWBMSL-UHFFFAOYSA-N 4-(3-hydroxy-2-methylanilino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC1=CC=CC(O)=C1C XFOAIBYWZWBMSL-UHFFFAOYSA-N 0.000 claims 2
- 206010061968 Gastric neoplasm Diseases 0.000 claims 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 2
- 230000031018 biological processes and functions Effects 0.000 claims 2
- 208000029742 colonic neoplasm Diseases 0.000 claims 2
- 208000037841 lung tumor Diseases 0.000 claims 2
- 208000025402 neoplasm of esophagus Diseases 0.000 claims 2
- 208000023983 oral cavity neoplasm Diseases 0.000 claims 2
- 208000023974 pharynx neoplasm Diseases 0.000 claims 2
- RLYNGYDVXRKEOO-XQHVRGAUSA-N (e)-but-2-enoic acid Chemical compound C\C=C\C(O)=O.C\C=C\C(O)=O RLYNGYDVXRKEOO-XQHVRGAUSA-N 0.000 claims 1
- XGQFVVQUVDLUAW-UHFFFAOYSA-N 3-[(3-cyano-6,7-dimethoxyquinolin-4-yl)amino]-2-methylbenzoic acid Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC1=CC=CC(C(O)=O)=C1C XGQFVVQUVDLUAW-UHFFFAOYSA-N 0.000 claims 1
- SMWDFEZZVXVKRB-WFVSFCRTSA-N 3-deuterioquinoline Chemical compound C1=CC=CC2=CC([2H])=CN=C21 SMWDFEZZVXVKRB-WFVSFCRTSA-N 0.000 claims 1
- TZNVNORLQOCTMY-UHFFFAOYSA-N 4-(2,4-dihydroxyanilino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC1=CC=C(O)C=C1O TZNVNORLQOCTMY-UHFFFAOYSA-N 0.000 claims 1
- FNAOGFPOADZWDT-UHFFFAOYSA-N 4-(2-amino-4,5-dimethylanilino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC1=CC(C)=C(C)C=C1N FNAOGFPOADZWDT-UHFFFAOYSA-N 0.000 claims 1
- GGSWVTQHMOCNJI-UHFFFAOYSA-N 4-(2-chloro-4-hydroxyanilino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC1=CC=C(O)C=C1Cl GGSWVTQHMOCNJI-UHFFFAOYSA-N 0.000 claims 1
- VVWPJQJYFBFVJH-UHFFFAOYSA-N 4-(2-hydroxy-4-methylanilino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC1=CC=C(C)C=C1O VVWPJQJYFBFVJH-UHFFFAOYSA-N 0.000 claims 1
- QUSXJYUXWFSQPQ-UHFFFAOYSA-N 4-(2-hydroxy-5-methylanilino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC1=CC(C)=CC=C1O QUSXJYUXWFSQPQ-UHFFFAOYSA-N 0.000 claims 1
- GCNKUJAIEDINLA-UHFFFAOYSA-N 4-(2-hydroxy-6-methylanilino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC1=C(C)C=CC=C1O GCNKUJAIEDINLA-UHFFFAOYSA-N 0.000 claims 1
- RUGCZQOSGFAGFE-UHFFFAOYSA-N 4-(3,4-dibromoanilino)-6-nitroquinoline-3-carbonitrile Chemical compound C12=CC([N+](=O)[O-])=CC=C2N=CC(C#N)=C1NC1=CC=C(Br)C(Br)=C1 RUGCZQOSGFAGFE-UHFFFAOYSA-N 0.000 claims 1
- MBEJRIMUDFCZSL-UHFFFAOYSA-N 4-(3,5-dibromo-4-hydroxyanilino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC1=CC(Br)=C(O)C(Br)=C1 MBEJRIMUDFCZSL-UHFFFAOYSA-N 0.000 claims 1
- YJBYKRFNOYCMSK-UHFFFAOYSA-N 4-(3,5-dichloro-4-hydroxyanilino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC1=CC(Cl)=C(O)C(Cl)=C1 YJBYKRFNOYCMSK-UHFFFAOYSA-N 0.000 claims 1
- XBFPRUXDYAQIOC-UHFFFAOYSA-N 4-(3-acetylanilino)-6,7-diethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OCC)C(OCC)=CC2=NC=C(C#N)C=1NC1=CC=CC(C(C)=O)=C1 XBFPRUXDYAQIOC-UHFFFAOYSA-N 0.000 claims 1
- MZQKSJFIOAVZJR-UHFFFAOYSA-N 4-(3-aminoanilino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC1=CC=CC(N)=C1 MZQKSJFIOAVZJR-UHFFFAOYSA-N 0.000 claims 1
- PVGQFSJIEXPGDS-UHFFFAOYSA-N 4-(3-azidoanilino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC1=CC=CC(N=[N+]=[N-])=C1 PVGQFSJIEXPGDS-UHFFFAOYSA-N 0.000 claims 1
- JCGYXRCAGZQKRK-UHFFFAOYSA-N 4-(3-bromo-4-fluoroanilino)-7-methoxy-6-nitroquinoline-3-carbonitrile Chemical compound C=12C=C([N+]([O-])=O)C(OC)=CC2=NC=C(C#N)C=1NC1=CC=C(F)C(Br)=C1 JCGYXRCAGZQKRK-UHFFFAOYSA-N 0.000 claims 1
- BOXDQGATHFGEIB-UHFFFAOYSA-N 4-(3-bromo-4-methylanilino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC1=CC=C(C)C(Br)=C1 BOXDQGATHFGEIB-UHFFFAOYSA-N 0.000 claims 1
- UHTFOMCCUZQBMM-UHFFFAOYSA-N 4-(3-bromoanilino)-5,8-dimethoxyquinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C(OC)=CC=C(OC)C2=C1NC1=CC=CC(Br)=C1 UHTFOMCCUZQBMM-UHFFFAOYSA-N 0.000 claims 1
- VXMFIYMOOZZNJO-UHFFFAOYSA-N 4-(3-bromoanilino)-6,7,8-trimethoxyquinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C(OC)=C(OC)C(OC)=CC2=C1NC1=CC=CC(Br)=C1 VXMFIYMOOZZNJO-UHFFFAOYSA-N 0.000 claims 1
- PADYONKQSSWAFW-UHFFFAOYSA-N 4-(3-bromoanilino)-6,7-dibutoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OCCCC)C(OCCCC)=CC2=NC=C(C#N)C=1NC1=CC=CC(Br)=C1 PADYONKQSSWAFW-UHFFFAOYSA-N 0.000 claims 1
- LRIHFKGXXJKDDD-UHFFFAOYSA-N 4-(3-bromoanilino)-6,7-dipropoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OCCC)C(OCCC)=CC2=NC=C(C#N)C=1NC1=CC=CC(Br)=C1 LRIHFKGXXJKDDD-UHFFFAOYSA-N 0.000 claims 1
- BWXDTMBEXXDSQD-UHFFFAOYSA-N 4-(3-bromoanilino)-6-(3-pyrrolidin-1-ylpropylamino)quinoline-3-carbonitrile Chemical compound BrC1=CC=CC(NC=2C3=CC(NCCCN4CCCC4)=CC=C3N=CC=2C#N)=C1 BWXDTMBEXXDSQD-UHFFFAOYSA-N 0.000 claims 1
- MCIICVWNGVSLPW-UHFFFAOYSA-N 4-(3-bromoanilino)-6-(dimethylamino)quinoline-3-carbonitrile;hydrochloride Chemical compound Cl.C12=CC(N(C)C)=CC=C2N=CC(C#N)=C1NC1=CC=CC(Br)=C1 MCIICVWNGVSLPW-UHFFFAOYSA-N 0.000 claims 1
- IYPAMCYSGUYVAN-UHFFFAOYSA-N 4-(3-bromoanilino)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1NC1=CC=CC(Br)=C1 IYPAMCYSGUYVAN-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D215/14—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/18—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
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US82660497A | 1997-04-03 | 1997-04-03 | |
PCT/US1998/006480 WO1998043960A1 (en) | 1997-04-03 | 1998-04-02 | Substituted 3-cyano quinolines |
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UA73073C2 true UA73073C2 (uk) | 2005-06-15 |
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UA99116029A UA73073C2 (uk) | 1997-04-03 | 1998-02-04 | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
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EP (1) | EP0973746B1 (ja) |
JP (2) | JP4537500B2 (ja) |
KR (1) | KR100531969B1 (ja) |
CN (1) | CN1121391C (ja) |
AR (1) | AR012313A1 (ja) |
AT (1) | ATE250583T1 (ja) |
AU (1) | AU750906B2 (ja) |
BR (1) | BR9808478A (ja) |
CA (1) | CA2285241C (ja) |
CZ (1) | CZ299136B6 (ja) |
DE (1) | DE69818442T2 (ja) |
DK (1) | DK0973746T3 (ja) |
ES (1) | ES2209124T3 (ja) |
HK (1) | HK1024917A1 (ja) |
HU (1) | HU229549B1 (ja) |
IL (1) | IL132192A0 (ja) |
NO (1) | NO313827B1 (ja) |
NZ (1) | NZ337782A (ja) |
PL (1) | PL196471B1 (ja) |
PT (1) | PT973746E (ja) |
RU (1) | RU2202551C2 (ja) |
SK (1) | SK284922B6 (ja) |
TR (1) | TR199902946T2 (ja) |
TW (1) | TWI228492B (ja) |
UA (1) | UA73073C2 (ja) |
WO (1) | WO1998043960A1 (ja) |
ZA (1) | ZA982771B (ja) |
Families Citing this family (366)
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NZ334125A (en) | 1996-09-25 | 2000-10-27 | Zeneca Ltd | Quinoline derivatives inhibiting the effect of growth factors such as VEGF |
GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
EP1005470B1 (en) | 1997-08-22 | 2007-08-01 | AstraZeneca AB | Oxindolylquinazoline derivatives as angiogenesis inhibitors |
BR9912672A (pt) | 1998-08-18 | 2002-06-11 | Univ California | Prevenção de produção de muco no trato respiratório por administração de antagonistas de egf-r |
US6297258B1 (en) | 1998-09-29 | 2001-10-02 | American Cyanamid Company | Substituted 3-cyanoquinolines |
SK287767B6 (sk) * | 1998-09-29 | 2011-09-05 | Wyeth Holdings Corporation | Substituovaný derivát 3-kyanochinolínu |
US6288082B1 (en) | 1998-09-29 | 2001-09-11 | American Cyanamid Company | Substituted 3-cyanoquinolines |
CN1165532C (zh) * | 1998-09-29 | 2004-09-08 | 惠氏控股有限公司 | 作为蛋白质酪氨酸激酶抑制剂的取代的3-氰基喹啉 |
AU2004200300A1 (en) * | 1998-09-29 | 2004-02-19 | Wyeth Holdings Corporation | Substituted 3-cyanoquinolines as Protein Tyrosine Kinases Inhibitors |
GB9904103D0 (en) | 1999-02-24 | 1999-04-14 | Zeneca Ltd | Quinoline derivatives |
US6972288B1 (en) * | 1999-02-27 | 2005-12-06 | Boehringer Ingelheim Pharma Kg | 4-amino-quinazoline and quinoline derivatives having an inhibitory effect on signal transduction mediated by tyrosine kinases |
CZ20013660A3 (cs) * | 1999-04-21 | 2002-01-16 | American Cyanamid Company | Substituované 3-kyano-(1,7),(1,5) a (1,8)-naftyridinové inhibitory tyrosinových kináz |
US6355636B1 (en) | 1999-04-21 | 2002-03-12 | American Cyanamid Company | Substituted 3-cyano-[1.7],[1.5], and [1.8] naphthyridine inhibitors of tyrosine kinases |
US6548496B2 (en) | 1999-04-21 | 2003-04-15 | American Cyanamid Company | Substituted 3-cyano-[1.7], [1.5], and [1.8] naphthyridine inhibitors of tyrosine kinases |
GB9910580D0 (en) * | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
GB9910579D0 (en) * | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
GB9910577D0 (en) * | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
NZ516633A (en) * | 1999-06-21 | 2004-09-24 | Boehringer Ingelheim Pharma | Bicyclic heterocycles, medicaments containing these compounds, their use and methods for the production thereof |
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