SK13752001A3 - Zlúčeniny s fúzovanými kruhmi a ich použitie ako liečiv - Google Patents
Zlúčeniny s fúzovanými kruhmi a ich použitie ako liečiv Download PDFInfo
- Publication number
- SK13752001A3 SK13752001A3 SK1375-2001A SK13752001A SK13752001A3 SK 13752001 A3 SK13752001 A3 SK 13752001A3 SK 13752001 A SK13752001 A SK 13752001A SK 13752001 A3 SK13752001 A3 SK 13752001A3
- Authority
- SK
- Slovakia
- Prior art keywords
- phenyl
- carboxylic acid
- benzimidazole
- cyclohexyl
- alkyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 339
- 239000003814 drug Substances 0.000 title claims abstract description 41
- 229940079593 drug Drugs 0.000 title description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 74
- 208000005176 Hepatitis C Diseases 0.000 claims abstract description 44
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 36
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 31
- -1 dimethylcarbamoyl Chemical group 0.000 claims description 570
- 125000001424 substituent group Chemical group 0.000 claims description 246
- 125000000217 alkyl group Chemical group 0.000 claims description 218
- 125000003118 aryl group Chemical group 0.000 claims description 109
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 109
- 238000004519 manufacturing process Methods 0.000 claims description 90
- 125000000623 heterocyclic group Chemical group 0.000 claims description 89
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 77
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 47
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 46
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 45
- 239000001257 hydrogen Substances 0.000 claims description 39
- 229910052757 nitrogen Inorganic materials 0.000 claims description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 37
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 35
- 125000005843 halogen group Chemical group 0.000 claims description 33
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 32
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 31
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 30
- 125000004076 pyridyl group Chemical group 0.000 claims description 27
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 26
- 125000004432 carbon atom Chemical group C* 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 22
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 19
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 18
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 18
- 239000004480 active ingredient Substances 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 16
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 16
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 239000001301 oxygen Substances 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 239000011593 sulfur Substances 0.000 claims description 15
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 239000003937 drug carrier Substances 0.000 claims description 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- 125000002541 furyl group Chemical group 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 11
- 125000001544 thienyl group Chemical group 0.000 claims description 11
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 10
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 10
- 239000008177 pharmaceutical agent Substances 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 9
- 229910052796 boron Inorganic materials 0.000 claims description 9
- 230000003612 virological effect Effects 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 7
- XHUKAVSDAIXUPI-UHFFFAOYSA-N ethyl 3-cyclohexyl-2-(4-phenylmethoxyphenyl)imidazo[1,2-a]pyridine-7-carboxylate Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C=1N=C2C=C(C(=O)OCC)C=CN2C=1C1CCCCC1 XHUKAVSDAIXUPI-UHFFFAOYSA-N 0.000 claims description 7
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 6
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 6
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 6
- MTLXNLQNSUOGRX-UHFFFAOYSA-N ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate Chemical compound C=1C=C(O)C=CC=1C1=NC2=CC(C(=O)OCC)=CC=C2N1C1CCCCC1 MTLXNLQNSUOGRX-UHFFFAOYSA-N 0.000 claims description 6
- GDKSUMHYXKBWRX-UHFFFAOYSA-N ethyl 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate Chemical compound C=1C=C(OC=2C=C(Br)C=CC=2)C=CC=1C1=NC2=CC(C(=O)OCC)=CC=C2N1C1CCCCC1 GDKSUMHYXKBWRX-UHFFFAOYSA-N 0.000 claims description 6
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 6
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 5
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 5
- MRHFHIDNFDSPHF-UHFFFAOYSA-N 1-cyclohexyl-2-[4-[(2-phenylphenyl)methoxy]phenyl]benzimidazole-5-carboxylic acid Chemical compound C=1C=C(OCC=2C(=CC=CC=2)C=2C=CC=CC=2)C=CC=1C1=NC2=CC(C(=O)O)=CC=C2N1C1CCCCC1 MRHFHIDNFDSPHF-UHFFFAOYSA-N 0.000 claims description 4
- GARFVWOEHHOKDL-UHFFFAOYSA-N 1-cyclopentyl-2-(4-phenylmethoxyphenyl)benzimidazole-5-carbonitrile Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C1=NC2=CC(C#N)=CC=C2N1C1CCCC1 GARFVWOEHHOKDL-UHFFFAOYSA-N 0.000 claims description 4
- MOBWPWFLKIDCCI-UHFFFAOYSA-N 1-cyclopentyl-2-(4-phenylmethoxyphenyl)benzimidazole-5-carboxylic acid Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C1=NC2=CC(C(=O)O)=CC=C2N1C1CCCC1 MOBWPWFLKIDCCI-UHFFFAOYSA-N 0.000 claims description 4
- 229940123066 Polymerase inhibitor Drugs 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 239000003443 antiviral agent Substances 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- IFXPSXVMNUYDAR-UHFFFAOYSA-N ethyl 1-cyclohexyl-2-(2-fluoro-4-hydroxyphenyl)benzimidazole-5-carboxylate Chemical compound C=1C=C(O)C=C(F)C=1C1=NC2=CC(C(=O)OCC)=CC=C2N1C1CCCCC1 IFXPSXVMNUYDAR-UHFFFAOYSA-N 0.000 claims description 4
- QGMLYCKHSRHZNW-UHFFFAOYSA-N ethyl 1-cyclohexyl-2-[4-(3-hydroxyphenoxy)phenyl]benzimidazole-5-carboxylate Chemical compound C=1C=C(OC=2C=C(O)C=CC=2)C=CC=1C1=NC2=CC(C(=O)OCC)=CC=C2N1C1CCCCC1 QGMLYCKHSRHZNW-UHFFFAOYSA-N 0.000 claims description 4
- KKSWXCUCIJCGET-BUHFOSPRSA-N ethyl 1-cyclohexyl-2-[4-[(e)-2-phenylethenyl]phenyl]benzimidazole-5-carboxylate Chemical compound C=1C=C(\C=C\C=2C=CC=CC=2)C=CC=1C1=NC2=CC(C(=O)OCC)=CC=C2N1C1CCCCC1 KKSWXCUCIJCGET-BUHFOSPRSA-N 0.000 claims description 4
- JQRDNQWNODGTJY-UHFFFAOYSA-N ethyl 1-cyclohexyl-2-[4-[3-(pyridin-4-ylmethoxy)phenoxy]phenyl]benzimidazole-5-carboxylate Chemical compound C=1C=C(OC=2C=C(OCC=3C=CN=CC=3)C=CC=2)C=CC=1C1=NC2=CC(C(=O)OCC)=CC=C2N1C1CCCCC1 JQRDNQWNODGTJY-UHFFFAOYSA-N 0.000 claims description 4
- DRGVBLBIKDAEOK-UHFFFAOYSA-N ethyl 1-cyclopentyl-2-(4-nitrophenyl)benzimidazole-5-carboxylate Chemical compound C=1C=C([N+]([O-])=O)C=CC=1C1=NC2=CC(C(=O)OCC)=CC=C2N1C1CCCC1 DRGVBLBIKDAEOK-UHFFFAOYSA-N 0.000 claims description 4
- OHTUBCOSOJXSHP-UHFFFAOYSA-N ethyl 2-(4-aminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate Chemical compound C=1C=C(N)C=CC=1C1=NC2=CC(C(=O)OCC)=CC=C2N1C1CCCC1 OHTUBCOSOJXSHP-UHFFFAOYSA-N 0.000 claims description 4
- DYWQXNDOGFMNQR-UHFFFAOYSA-N ethyl 2-(4-benzamidophenyl)-1-cyclopentylbenzimidazole-5-carboxylate Chemical compound C=1C=C(NC(=O)C=2C=CC=CC=2)C=CC=1C1=NC2=CC(C(=O)OCC)=CC=C2N1C1CCCC1 DYWQXNDOGFMNQR-UHFFFAOYSA-N 0.000 claims description 4
- DAUBKNDBDVZZJO-UHFFFAOYSA-N ethyl 2-[4-(3-acetyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate Chemical compound C=1C=C(OC=2C=C(OC(C)=O)C=CC=2)C=CC=1C1=NC2=CC(C(=O)OCC)=CC=C2N1C1CCCCC1 DAUBKNDBDVZZJO-UHFFFAOYSA-N 0.000 claims description 4
- ALZXFDJSCDICDR-UHFFFAOYSA-N ethyl 2-[4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate Chemical compound C=1C=C(OC(C=2C=C(F)C=CC=2)C=2C=C(F)C=CC=2)C=C(F)C=1C1=NC2=CC(C(=O)OCC)=CC=C2N1C1CCCCC1 ALZXFDJSCDICDR-UHFFFAOYSA-N 0.000 claims description 4
- OAUCINXZBRAATR-UHFFFAOYSA-N methyl 2-[4-[[2-(4-chlorophenyl)-5-[(2-methylpropan-2-yl)oxycarbonyl]phenyl]methoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylate Chemical compound C=1C=C(OCC=2C(=CC=C(C=2)C(=O)OC(C)(C)C)C=2C=CC(Cl)=CC=2)C=CC=1C1=NC2=CC(C(=O)OC)=CC=C2N1C1CCCCC1 OAUCINXZBRAATR-UHFFFAOYSA-N 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 3
- JSRFMRPPAJXOIQ-UHFFFAOYSA-N 1-cyclohexyl-2-[4-[3-(pyridin-4-ylmethoxy)phenoxy]phenyl]benzimidazole-5-carboxylic acid Chemical compound C=1C=C(OC=2C=C(OCC=3C=CN=CC=3)C=CC=2)C=CC=1C1=NC2=CC(C(=O)O)=CC=C2N1C1CCCCC1 JSRFMRPPAJXOIQ-UHFFFAOYSA-N 0.000 claims description 3
- UCPDXNWHPGCMAL-UHFFFAOYSA-N 1-cyclohexyl-2-[4-[[4-(4-fluorophenyl)-2-methyl-1,3-thiazol-5-yl]methoxy]phenyl]benzimidazole-5-carboxylic acid Chemical compound S1C(C)=NC(C=2C=CC(F)=CC=2)=C1COC(C=C1)=CC=C1C1=NC2=CC(C(O)=O)=CC=C2N1C1CCCCC1 UCPDXNWHPGCMAL-UHFFFAOYSA-N 0.000 claims description 3
- XWAJEYPTLLBHCD-UHFFFAOYSA-N 1-cyclopentyl-2-(4-phenylmethoxyphenyl)benzimidazole-5-carboxamide Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C1=NC2=CC(C(=O)N)=CC=C2N1C1CCCC1 XWAJEYPTLLBHCD-UHFFFAOYSA-N 0.000 claims description 3
- JLAAGFBZARTOSG-UHFFFAOYSA-N 1-cyclopentyl-2-[4-(pyridin-4-ylmethoxy)phenyl]benzimidazole-5-carboxylic acid;hydrochloride Chemical compound Cl.C=1C=C(OCC=2C=CN=CC=2)C=CC=1C1=NC2=CC(C(=O)O)=CC=C2N1C1CCCC1 JLAAGFBZARTOSG-UHFFFAOYSA-N 0.000 claims description 3
- FLFPCZPXGFXZQW-UHFFFAOYSA-N 1-cyclopentyl-n'-hydroxy-2-(4-phenylmethoxyphenyl)benzimidazole-5-carboximidamide Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C1=NC2=CC(C(=NO)N)=CC=C2N1C1CCCC1 FLFPCZPXGFXZQW-UHFFFAOYSA-N 0.000 claims description 3
- MQZXYJRCIONLHP-UHFFFAOYSA-N 2-[2-chloro-4-(4-phenylmethoxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C=1C=C(OC=2C=CC(OCC=3C=CC=CC=3)=CC=2)C=C(Cl)C=1C1=NC2=CC(C(=O)O)=CC=C2N1C1CCCCC1 MQZXYJRCIONLHP-UHFFFAOYSA-N 0.000 claims description 3
- UWVTWPISRDLYEL-UHFFFAOYSA-N 2-[4-[3-(3-chlorophenyl)phenoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C=1C=C(OC=2C=C(C=CC=2)C=2C=C(Cl)C=CC=2)C=CC=1C1=NC2=CC(C(=O)O)=CC=C2N1C1CCCCC1 UWVTWPISRDLYEL-UHFFFAOYSA-N 0.000 claims description 3
- KSCPIFPNRGZFRV-UHFFFAOYSA-N 2-[4-[[2-(4-chlorophenyl)-5-methoxyphenyl]methoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C=1C(OC)=CC=C(C=2C=CC(Cl)=CC=2)C=1COC(C=C1)=CC=C1C1=NC2=CC(C(O)=O)=CC=C2N1C1CCCCC1 KSCPIFPNRGZFRV-UHFFFAOYSA-N 0.000 claims description 3
- NUTVDFXSAWDYJI-UHFFFAOYSA-N 2-[4-[[2-(4-chlorophenyl)-5-methoxyphenyl]methoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid;hydrochloride Chemical compound Cl.C=1C(OC)=CC=C(C=2C=CC(Cl)=CC=2)C=1COC(C=C1)=CC=C1C1=NC2=CC(C(O)=O)=CC=C2N1C1CCCCC1 NUTVDFXSAWDYJI-UHFFFAOYSA-N 0.000 claims description 3
- BLDMYGXHGQDUQD-UHFFFAOYSA-N 2-[4-[[2-(4-chlorophenyl)-5-methoxyphenyl]methoxy]phenyl]-1-cyclohexylindole-5-carboxylic acid Chemical compound C=1C(OC)=CC=C(C=2C=CC(Cl)=CC=2)C=1COC(C=C1)=CC=C1C1=CC2=CC(C(O)=O)=CC=C2N1C1CCCCC1 BLDMYGXHGQDUQD-UHFFFAOYSA-N 0.000 claims description 3
- CRRUDWMTYYAPJT-UHFFFAOYSA-N 2-[4-[[5-chloro-2-(4-chlorophenyl)phenyl]methoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C=1C=C(OCC=2C(=CC=C(Cl)C=2)C=2C=CC(Cl)=CC=2)C=CC=1C1=NC2=CC(C(=O)O)=CC=C2N1C1CCCCC1 CRRUDWMTYYAPJT-UHFFFAOYSA-N 0.000 claims description 3
- XEXJQBMKIBNZOB-SOAUALDESA-N C1C[C@@H](C(C)(C)C)CC[C@@H]1N1C2=CC=C(C(O)=O)C=C2N=C1C(C=C1)=CC=C1OCC1=CC=CC=C1 Chemical compound C1C[C@@H](C(C)(C)C)CC[C@@H]1N1C2=CC=C(C(O)=O)C=C2N=C1C(C=C1)=CC=C1OCC1=CC=CC=C1 XEXJQBMKIBNZOB-SOAUALDESA-N 0.000 claims description 3
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 3
- 125000004450 alkenylene group Chemical group 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- DQTCYQWOJFUQLB-UHFFFAOYSA-N ethyl 2-[4-[(2-bromo-5-chlorophenyl)methoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylate Chemical compound C=1C=C(OCC=2C(=CC=C(Cl)C=2)Br)C=CC=1C1=NC2=CC(C(=O)OCC)=CC=C2N1C1CCCCC1 DQTCYQWOJFUQLB-UHFFFAOYSA-N 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 claims description 2
- DOMQFIFVDIAOOT-ROUUACIJSA-N (2S,3R)-N-[4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-1,2,4-triazol-3-yl]-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide Chemical compound COC1=C(C(=CC=C1)OC)N1C(=NN=C1C=1C=NC=C(C=1)C)NS(=O)(=O)[C@@H](C)[C@H](C)C1=NC=C(C=N1)C DOMQFIFVDIAOOT-ROUUACIJSA-N 0.000 claims description 2
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 claims description 2
- UKGJZDSUJSPAJL-YPUOHESYSA-N (e)-n-[(1r)-1-[3,5-difluoro-4-(methanesulfonamido)phenyl]ethyl]-3-[2-propyl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enamide Chemical compound CCCC1=NC(C(F)(F)F)=CC=C1\C=C\C(=O)N[C@H](C)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 UKGJZDSUJSPAJL-YPUOHESYSA-N 0.000 claims description 2
- ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 claims description 2
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 claims description 2
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 claims description 2
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- OFHCEFRZRAWBIL-UHFFFAOYSA-N 2-[4-[2-(carboxymethoxy)phenoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound OC(=O)COC1=CC=CC=C1OC1=CC=C(C=2N(C3=CC=C(C=C3N=2)C(O)=O)C2CCCCC2)C=C1 OFHCEFRZRAWBIL-UHFFFAOYSA-N 0.000 claims description 2
- QAXNUTJNSYRORY-UHFFFAOYSA-N 2-[4-[2-[(1-acetylpiperidin-4-yl)methoxy]phenoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C1CN(C(=O)C)CCC1COC1=CC=CC=C1OC1=CC=C(C=2N(C3=CC=C(C=C3N=2)C(O)=O)C2CCCCC2)C=C1 QAXNUTJNSYRORY-UHFFFAOYSA-N 0.000 claims description 2
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- LVNGMYXNYMOQOQ-UHFFFAOYSA-N 2-[4-[3-(carboxymethoxy)phenoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound OC(=O)COC1=CC=CC(OC=2C=CC(=CC=2)C=2N(C3=CC=C(C=C3N=2)C(O)=O)C2CCCCC2)=C1 LVNGMYXNYMOQOQ-UHFFFAOYSA-N 0.000 claims description 2
- NAFAMXHSUSTFPP-UHFFFAOYSA-N 2-[4-[3-[(1-acetylpiperidin-4-yl)methoxy]phenoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C1CN(C(=O)C)CCC1COC1=CC=CC(OC=2C=CC(=CC=2)C=2N(C3=CC=C(C=C3N=2)C(O)=O)C2CCCCC2)=C1 NAFAMXHSUSTFPP-UHFFFAOYSA-N 0.000 claims description 2
- VBGOZRMOBZKKSM-UHFFFAOYSA-N 2-[4-[3-[(2-chlorophenyl)methoxy]phenoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C=1C=C(OC=2C=C(OCC=3C(=CC=CC=3)Cl)C=CC=2)C=CC=1C1=NC2=CC(C(=O)O)=CC=C2N1C1CCCCC1 VBGOZRMOBZKKSM-UHFFFAOYSA-N 0.000 claims description 2
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- FEQGTHBVQQPSQE-UHFFFAOYSA-N 2-[4-[3-[(4-chlorophenyl)methoxy]phenoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C=1C=C(OC=2C=C(OCC=3C=CC(Cl)=CC=3)C=CC=2)C=CC=1C1=NC2=CC(C(=O)O)=CC=C2N1C1CCCCC1 FEQGTHBVQQPSQE-UHFFFAOYSA-N 0.000 claims description 2
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- ORQHYXOSCUENHB-NDEPHWFRSA-N 2-[4-[[(2s)-1-(4-acetamidophenyl)pyrrolidin-2-yl]methoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C1=CC(NC(=O)C)=CC=C1N1[C@H](COC=2C=CC(=CC=2)C=2N(C3=CC=C(C=C3N=2)C(O)=O)C2CCCCC2)CCC1 ORQHYXOSCUENHB-NDEPHWFRSA-N 0.000 claims description 2
- RHJRQAJKEVTTBI-SANMLTNESA-N 2-[4-[[(2s)-1-benzoylpyrrolidin-2-yl]methoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C=1C=C(OC[C@H]2N(CCC2)C(=O)C=2C=CC=CC=2)C=CC=1C1=NC2=CC(C(=O)O)=CC=C2N1C1CCCCC1 RHJRQAJKEVTTBI-SANMLTNESA-N 0.000 claims description 2
- PUSHYSWVVRETFX-MHZLTWQESA-N 2-[4-[[(2s)-1-benzylpyrrolidin-2-yl]methoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C=1C=C(OC[C@H]2N(CCC2)CC=2C=CC=CC=2)C=CC=1C1=NC2=CC(C(=O)O)=CC=C2N1C1CCCCC1 PUSHYSWVVRETFX-MHZLTWQESA-N 0.000 claims description 2
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- FSCIOEAQSHSDMS-UHFFFAOYSA-N 2-[4-[[2-(4-carbamoylphenyl)-5-chlorophenyl]methoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C1=CC(C(=O)N)=CC=C1C1=CC=C(Cl)C=C1COC1=CC=C(C=2N(C3=CC=C(C=C3N=2)C(O)=O)C2CCCCC2)C=C1 FSCIOEAQSHSDMS-UHFFFAOYSA-N 0.000 claims description 2
- KCQLAJFCUNNGOR-UHFFFAOYSA-N 2-[4-[[2-(4-carboxyphenyl)-5-chlorophenyl]methoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=C(Cl)C=C1COC1=CC=C(C=2N(C3=CC=C(C=C3N=2)C(O)=O)C2CCCCC2)C=C1 KCQLAJFCUNNGOR-UHFFFAOYSA-N 0.000 claims description 2
- CBZNLRDZEVRORY-UHFFFAOYSA-N 2-[4-[[2-(4-carboxyphenyl)-5-methoxyphenyl]methoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C=1C(OC)=CC=C(C=2C=CC(=CC=2)C(O)=O)C=1COC(C=C1)=CC=C1C1=NC2=CC(C(O)=O)=CC=C2N1C1CCCCC1 CBZNLRDZEVRORY-UHFFFAOYSA-N 0.000 claims description 2
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- LAEZWCBQIRVMAX-UHFFFAOYSA-N 2-[4-[[2-(4-chlorophenyl)-4-(2h-tetrazol-5-yl)phenyl]methoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C=1C=C(OCC=2C(=CC(=CC=2)C=2NN=NN=2)C=2C=CC(Cl)=CC=2)C=CC=1C1=NC2=CC(C(=O)O)=CC=C2N1C1CCCCC1 LAEZWCBQIRVMAX-UHFFFAOYSA-N 0.000 claims description 2
- YZELIVBJMZEPJZ-UHFFFAOYSA-N 2-[4-[[2-(4-chlorophenyl)-5-(cyclohexylmethylcarbamoyl)phenyl]methoxy]-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid;hydrochloride Chemical compound Cl.C=1C=C(OCC=2C(=CC=C(C=2)C(=O)NCC2CCCCC2)C=2C=CC(Cl)=CC=2)C=C(F)C=1C1=NC2=CC(C(=O)O)=CC=C2N1C1CCCCC1 YZELIVBJMZEPJZ-UHFFFAOYSA-N 0.000 claims description 2
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- NQXHREGQRASHRG-UHFFFAOYSA-N 2-[4-[[2-(4-chlorophenyl)-5-ethoxycarbonylphenyl]methoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C=1C(C(=O)OCC)=CC=C(C=2C=CC(Cl)=CC=2)C=1COC(C=C1)=CC=C1C1=NC2=CC(C(O)=O)=CC=C2N1C1CCCCC1 NQXHREGQRASHRG-UHFFFAOYSA-N 0.000 claims description 2
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- VXMQKWPKLXXJSM-UHFFFAOYSA-N 2-[4-[[2-(4-chlorophenyl)-5-methoxyphenyl]methoxy]-2-fluorophenyl]-1-(1,1-dioxothian-4-yl)benzimidazole-5-carboxylic acid Chemical compound C=1C(OC)=CC=C(C=2C=CC(Cl)=CC=2)C=1COC(C=C1F)=CC=C1C1=NC2=CC(C(O)=O)=CC=C2N1C1CCS(=O)(=O)CC1 VXMQKWPKLXXJSM-UHFFFAOYSA-N 0.000 claims description 2
- UXGVPMIJNGPSCU-UHFFFAOYSA-N 2-[4-[[2-(4-chlorophenyl)-5-methoxyphenyl]methoxy]-2-fluorophenyl]-1-(1-oxothian-4-yl)benzimidazole-5-carboxylic acid Chemical compound C=1C(OC)=CC=C(C=2C=CC(Cl)=CC=2)C=1COC(C=C1F)=CC=C1C1=NC2=CC(C(O)=O)=CC=C2N1C1CCS(=O)CC1 UXGVPMIJNGPSCU-UHFFFAOYSA-N 0.000 claims description 2
- WUEYYZVDQIDZDX-UHFFFAOYSA-N 2-[4-[[2-(4-chlorophenyl)-5-methoxyphenyl]methoxy]-2-fluorophenyl]-1-(thian-4-yl)benzimidazole-5-carboxylic acid Chemical compound C=1C(OC)=CC=C(C=2C=CC(Cl)=CC=2)C=1COC(C=C1F)=CC=C1C1=NC2=CC(C(O)=O)=CC=C2N1C1CCSCC1 WUEYYZVDQIDZDX-UHFFFAOYSA-N 0.000 claims description 2
- WLCWTESMZNKVIE-UHFFFAOYSA-N 2-[4-[[2-(4-chlorophenyl)-5-methoxyphenyl]methoxy]phenyl]-1-(1,1-dioxothian-4-yl)benzimidazole-5-carboxylic acid Chemical compound C=1C(OC)=CC=C(C=2C=CC(Cl)=CC=2)C=1COC(C=C1)=CC=C1C1=NC2=CC(C(O)=O)=CC=C2N1C1CCS(=O)(=O)CC1 WLCWTESMZNKVIE-UHFFFAOYSA-N 0.000 claims description 2
- VUAAGCRVRJUJIT-UHFFFAOYSA-N 2-[4-[[2-(4-chlorophenyl)-5-methoxyphenyl]methoxy]phenyl]-1-(1-oxothian-4-yl)benzimidazole-5-carboxylic acid Chemical compound C=1C(OC)=CC=C(C=2C=CC(Cl)=CC=2)C=1COC(C=C1)=CC=C1C1=NC2=CC(C(O)=O)=CC=C2N1C1CCS(=O)CC1 VUAAGCRVRJUJIT-UHFFFAOYSA-N 0.000 claims description 2
- XLRVQPGTSCYBGX-UHFFFAOYSA-N 2-[4-[[2-(4-chlorophenyl)-5-methoxyphenyl]methoxy]phenyl]-1-(thian-4-yl)benzimidazole-5-carboxylic acid Chemical compound C=1C(OC)=CC=C(C=2C=CC(Cl)=CC=2)C=1COC(C=C1)=CC=C1C1=NC2=CC(C(O)=O)=CC=C2N1C1CCSCC1 XLRVQPGTSCYBGX-UHFFFAOYSA-N 0.000 claims description 2
- FDXHQOXCSBBZIP-UHFFFAOYSA-N 2-[4-[[2-(4-chlorophenyl)-5-methoxyphenyl]methoxy]phenyl]-1-cyclohexylbenzimidazole-4-carboxylic acid Chemical compound C=1C(OC)=CC=C(C=2C=CC(Cl)=CC=2)C=1COC(C=C1)=CC=C1C1=NC2=C(C(O)=O)C=CC=C2N1C1CCCCC1 FDXHQOXCSBBZIP-UHFFFAOYSA-N 0.000 claims description 2
- GJYBEMWKVRJIFR-UHFFFAOYSA-N 2-[4-[[2-(4-chlorophenyl)-5-methoxyphenyl]methoxy]phenyl]-1-cyclohexylbenzimidazole-5-sulfonic acid Chemical compound C=1C(OC)=CC=C(C=2C=CC(Cl)=CC=2)C=1COC(C=C1)=CC=C1C1=NC2=CC(S(O)(=O)=O)=CC=C2N1C1CCCCC1 GJYBEMWKVRJIFR-UHFFFAOYSA-N 0.000 claims description 2
- XCLRTNDTFJQVAD-UHFFFAOYSA-N 2-[4-[[2-(4-chlorophenyl)-5-methoxyphenyl]methoxy]phenyl]-3-cyclohexylbenzimidazole-4-carboxylic acid Chemical compound C=1C(OC)=CC=C(C=2C=CC(Cl)=CC=2)C=1COC(C=C1)=CC=C1C1=NC2=CC=CC(C(O)=O)=C2N1C1CCCCC1 XCLRTNDTFJQVAD-UHFFFAOYSA-N 0.000 claims description 2
- GCVMAWCICPRBIZ-UHFFFAOYSA-N 2-[4-[[2-(4-chlorophenyl)-5-methylsulfanylphenyl]methoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid Chemical compound C=1C(SC)=CC=C(C=2C=CC(Cl)=CC=2)C=1COC(C=C1)=CC=C1C1=NC2=CC(C(O)=O)=CC=C2N1C1CCCCC1 GCVMAWCICPRBIZ-UHFFFAOYSA-N 0.000 claims description 2
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- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 125000005969 isothiazolinyl group Chemical group 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
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- 229940039717 lanolin Drugs 0.000 description 1
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- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
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- 230000020477 pH reduction Effects 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
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- NIXKBAZVOQAHGC-UHFFFAOYSA-N phenylmethanesulfonic acid Chemical compound OS(=O)(=O)CC1=CC=CC=C1 NIXKBAZVOQAHGC-UHFFFAOYSA-N 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- XBXHCBLBYQEYTI-UHFFFAOYSA-N piperidin-4-ylmethanol Chemical compound OCC1CCNCC1 XBXHCBLBYQEYTI-UHFFFAOYSA-N 0.000 description 1
- IZXWMVPZODQBRB-UHFFFAOYSA-N piperidine-3,4-diol Chemical compound OC1CCNCC1O IZXWMVPZODQBRB-UHFFFAOYSA-N 0.000 description 1
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- 239000002243 precursor Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 238000000746 purification Methods 0.000 description 1
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- 235000010265 sodium sulphite Nutrition 0.000 description 1
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- 239000003381 stabilizer Substances 0.000 description 1
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- 229910052623 talc Inorganic materials 0.000 description 1
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- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
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- RIHBTHGKWXRWQX-UHFFFAOYSA-N tert-butyl 4-bromo-3-methylbenzoate Chemical compound CC1=CC(C(=O)OC(C)(C)C)=CC=C1Br RIHBTHGKWXRWQX-UHFFFAOYSA-N 0.000 description 1
- NOUFUCBMRFTXNS-UHFFFAOYSA-N tert-butyl 4-bromo-3-methylbenzoate;methyl 2-[4-[[2-bromo-5-[(2-methylpropan-2-yl)oxycarbonyl]phenyl]methoxy]phenyl]-1-cyclohexylbenzimidazole-5-carboxylate Chemical compound CC1=CC(C(=O)OC(C)(C)C)=CC=C1Br.C=1C=C(OCC=2C(=CC=C(C=2)C(=O)OC(C)(C)C)Br)C=CC=1C1=NC2=CC(C(=O)OC)=CC=C2N1C1CCCCC1 NOUFUCBMRFTXNS-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- XOGGUFAVLNCTRS-UHFFFAOYSA-N tetrapotassium;iron(2+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] XOGGUFAVLNCTRS-UHFFFAOYSA-N 0.000 description 1
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- 239000002562 thickening agent Substances 0.000 description 1
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- 239000011135 tin Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 description 1
- AISMNBXOJRHCIA-UHFFFAOYSA-N trimethylazanium;bromide Chemical compound Br.CN(C)C AISMNBXOJRHCIA-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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| JP36900899 | 1999-12-27 | ||
| PCT/JP2000/009181 WO2001047883A1 (fr) | 1999-12-27 | 2000-12-22 | Composes a cycles accoles et leur utilisation comme medicaments |
| JP2000391904A JP2001247550A (ja) | 1999-12-27 | 2000-12-25 | 縮合環化合物及びその医薬用途 |
| JP2001193786 | 2001-06-26 | ||
| JP2001351537 | 2001-11-16 |
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| AU2002346216B2 (en) * | 1999-12-27 | 2005-12-08 | Japan Tobacco Inc. | Fused cyclic compounds and medicinal use thereof |
| US6770666B2 (en) | 1999-12-27 | 2004-08-03 | Japan Tobacco Inc. | Fused-ring compounds and use thereof as drugs |
| US6448281B1 (en) * | 2000-07-06 | 2002-09-10 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
| US8481712B2 (en) | 2001-01-22 | 2013-07-09 | Merck Sharp & Dohme Corp. | Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase |
| EP1539188B1 (en) * | 2001-01-22 | 2015-01-07 | Merck Sharp & Dohme Corp. | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| JP2004534026A (ja) * | 2001-05-05 | 2004-11-11 | スミスクライン ビーチャム パブリック リミテッド カンパニー | オレキシン受容体アンタゴニストとしてのn−アロイルサイクリックアミン誘導体 |
| AR035543A1 (es) * | 2001-06-26 | 2004-06-16 | Japan Tobacco Inc | Agente terapeutico para la hepatitis c que comprende un compuesto de anillo condensado, compuesto de anillo condensado, composicion farmaceutica que lo comprende, compuestos de benzimidazol, tiazol y bifenilo utiles como intermediarios para producir dichos compuestos, uso del compuesto de anillo con |
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| DE10135050A1 (de) * | 2001-07-09 | 2003-02-06 | Schering Ag | 1-Ary1-2-N-, S- oder O-substituierte Benzimidazolderivate, deren Verwendung zur Herstellung von Arzneimitteln sowie diese Derivate enthaltende pharmazeutische Präparate |
| US6903126B2 (en) | 2001-07-09 | 2005-06-07 | Schering Ag | 1-Aryl-2-N-, S- or O-substituted benzimidazole derivatives, their use for the production of pharmaceutical agents as well as pharmaceutical preparations that contain these derivatives |
| CA2448737C (en) | 2001-07-20 | 2010-06-01 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
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| US7294457B2 (en) * | 2001-08-07 | 2007-11-13 | Boehringer Ingelheim (Canada) Ltd. | Direct binding assay for identifying inhibitors of HCV polymerase |
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| BR0308537A (pt) | 2002-03-20 | 2005-02-09 | Metabolex Inc | Composto, composição, e métodos para tratar diabetes tipo 2 e hiperuricemia, para modular resistência a insulina e para aliviar hiperlipidemia em um indivìduo e agente de prodroga |
| EP1506000B9 (en) | 2002-05-20 | 2011-08-31 | Bristol-Myers Squibb Company | Heterocyclicsulfonamide hepatitis c virus inhibitors |
| MY140680A (en) | 2002-05-20 | 2010-01-15 | Bristol Myers Squibb Co | Hepatitis c virus inhibitors |
| ES2361011T3 (es) | 2002-05-20 | 2011-06-13 | Bristol-Myers Squibb Company | Inhibidores del virus de la hepatitis c. |
| AU2003301959A1 (en) | 2002-05-20 | 2004-06-03 | Bristol-Myers Squibb Company | Substituted cycloalkyl p1' hepatitis c virus inhibitors |
| ATE389656T1 (de) * | 2002-06-04 | 2008-04-15 | Neogenesis Pharmaceuticals Inc | Pyrazolo(1,5-a)pyrimidin-verbindungen als antivirale agentien |
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| KR20050067383A (ko) | 2002-08-06 | 2005-07-01 | 아스트라제네카 아베 | Tie2(tek) 활성을 갖는 축합 피리딘 및 피리미딘 |
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| DE10300398A1 (de) * | 2003-01-09 | 2004-07-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verwendung von substituierten 2-Phenylbenzimidazolen als Arzneimittel |
| US7151114B2 (en) | 2003-01-09 | 2006-12-19 | Boehringer Ingelheim International Gmbh | Use of substituted 2-phenylbenzimidazoles as medicaments |
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| US7199259B2 (en) | 2003-06-20 | 2007-04-03 | Metabolex, Inc. | Resolution of α-(phenoxy)phenylacetic acid derivatives |
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| US7112601B2 (en) | 2003-09-11 | 2006-09-26 | Bristol-Myers Squibb Company | Cycloalkyl heterocycles for treating hepatitis C virus |
| NZ545864A (en) | 2003-09-22 | 2009-12-24 | S Bio Pte Ltd | Benzimidazole derivates: preparation and pharmaceutical applications |
| MXPA06003141A (es) | 2003-09-22 | 2006-06-05 | Boehringer Ingelheim Int | Peptidos macrociclicos activos contra el virus de la hepatitis c. |
| US7358259B2 (en) | 2003-09-26 | 2008-04-15 | Rigel Pharmaceuticals, Inc. | HCV inhibitors and methods of using them |
| GB0323845D0 (en) * | 2003-10-10 | 2003-11-12 | Angeletti P Ist Richerche Bio | Chemical compounds,compositions and uses |
| RS20060259A (sr) | 2003-10-14 | 2008-08-07 | Intermune Inc., | Makrociklične karboksilne kiseline i acilsulfonamidi kao inhibitori replikacije hcv |
| US7132504B2 (en) | 2003-11-12 | 2006-11-07 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7135462B2 (en) | 2003-11-20 | 2006-11-14 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
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- 2000-12-22 EP EP00987728A patent/EP1162196A4/en not_active Withdrawn
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| NZ514403A (en) | 2002-10-25 |
| CN1342145A (zh) | 2002-03-27 |
| AU763356C (en) | 2004-08-26 |
| NO20014134D0 (no) | 2001-08-24 |
| HUP0202263A2 (hu) | 2002-12-28 |
| HUP0202263A3 (en) | 2003-02-28 |
| NO20014134L (no) | 2001-10-22 |
| EP1162196A4 (en) | 2003-04-16 |
| CA2363274A1 (en) | 2001-07-05 |
| ZA200107870B (en) | 2002-09-25 |
| AR031230A1 (es) | 2003-09-17 |
| AU763356B2 (en) | 2003-07-17 |
| AU2401701A (en) | 2001-07-09 |
| TR200103147T1 (tr) | 2002-06-21 |
| CN1167680C (zh) | 2004-09-22 |
| IL145071A0 (en) | 2002-06-30 |
| CN1623984A (zh) | 2005-06-08 |
| US20070032497A1 (en) | 2007-02-08 |
| US7112600B1 (en) | 2006-09-26 |
| ID30204A (id) | 2001-11-15 |
| WO2001047883A1 (fr) | 2001-07-05 |
| EP1162196A1 (en) | 2001-12-12 |
| CZ20013424A3 (cs) | 2002-02-13 |
| RU2223761C2 (ru) | 2004-02-20 |
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