JP2014520118A5 - - Google Patents
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- Publication number
- JP2014520118A5 JP2014520118A5 JP2014516015A JP2014516015A JP2014520118A5 JP 2014520118 A5 JP2014520118 A5 JP 2014520118A5 JP 2014516015 A JP2014516015 A JP 2014516015A JP 2014516015 A JP2014516015 A JP 2014516015A JP 2014520118 A5 JP2014520118 A5 JP 2014520118A5
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- azaspiro
- oxa
- alkyl
- benzo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 125000000217 alkyl group Chemical group 0.000 claims 51
- 239000001257 hydrogen Substances 0.000 claims 22
- 229910052739 hydrogen Inorganic materials 0.000 claims 22
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 15
- 125000001475 halogen functional group Chemical group 0.000 claims 11
- 150000002431 hydrogen Chemical class 0.000 claims 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 9
- 229910052799 carbon Inorganic materials 0.000 claims 9
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims 9
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 9
- 150000001875 compounds Chemical class 0.000 claims 8
- 125000004432 carbon atom Chemical group C* 0.000 claims 6
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 5
- 239000008194 pharmaceutical composition Substances 0.000 claims 5
- 150000003839 salts Chemical class 0.000 claims 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 3
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 3
- 229910052757 nitrogen Inorganic materials 0.000 claims 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 3
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 claims 3
- 239000001301 oxygen Substances 0.000 claims 3
- 229910052760 oxygen Inorganic materials 0.000 claims 3
- 125000003386 piperidinyl group Chemical group 0.000 claims 3
- 125000001424 substituent group Chemical group 0.000 claims 3
- 125000003554 tetrahydropyrrolyl group Chemical group 0.000 claims 3
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims 2
- CJONRBPKDVXYNI-AOMKIAJQSA-N (5s,7s)-3-(3-methoxy-2,2-dimethylpropyl)-7-[[6-(trifluoromethyl)benzimidazol-1-yl]methyl]-1-oxa-3-azaspiro[4.5]decan-2-one Chemical compound O1C(=O)N(CC(C)(C)COC)C[C@]11C[C@@H](CN2C3=CC(=CC=C3N=C2)C(F)(F)F)CCC1 CJONRBPKDVXYNI-AOMKIAJQSA-N 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- MUWXYMROALAJBA-UHFFFAOYSA-N 3-(2,2-dimethylpropyl)-7-[[6-(trifluoromethyl)benzimidazol-1-yl]methyl]-1-oxa-3-azaspiro[4.5]decan-2-one Chemical compound O1C(=O)N(CC(C)(C)C)CC11CC(CN2C3=CC(=CC=C3N=C2)C(F)(F)F)CCC1 MUWXYMROALAJBA-UHFFFAOYSA-N 0.000 claims 1
- UZMHIQKQQQRBNC-KSSFIOAISA-N 3-[[(5s,7s)-2-oxo-3-(2,2,3,3,3-pentafluoropropyl)-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(F)(F)C(F)(F)F)C[C@]11C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1 UZMHIQKQQQRBNC-KSSFIOAISA-N 0.000 claims 1
- JRRWNQNLRSHLLF-UWJYYQICSA-N 3-[[(5s,7s)-2-oxo-3-(trimethylsilylmethyl)-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(C[Si](C)(C)C)C[C@]11C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1 JRRWNQNLRSHLLF-UWJYYQICSA-N 0.000 claims 1
- XCFXGHDRQCFVFF-CPJSRVTESA-N 3-[[(5s,7s)-3-(2,2-dimethyl-3-propan-2-yloxypropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)COC(C)C)C[C@]11C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1 XCFXGHDRQCFVFF-CPJSRVTESA-N 0.000 claims 1
- SWQFFJVGEHZGRF-JTSKRJEESA-N 3-[[(5s,7s)-3-(2,2-dimethylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)C)C[C@]11C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1 SWQFFJVGEHZGRF-JTSKRJEESA-N 0.000 claims 1
- HAPYNQDQYINPTB-GOTSBHOMSA-N 3-[[(5s,7s)-3-(2,2-dimethylpropyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)C)C[C@]11C[C@@](C)(CN2C3=CC(=CC=C3N=C2)C#N)CCC1 HAPYNQDQYINPTB-GOTSBHOMSA-N 0.000 claims 1
- OUUALNNPVZBRNV-JTSKRJEESA-N 3-[[(5s,7s)-3-(2-cyano-2-methylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)C#N)C[C@]11C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1 OUUALNNPVZBRNV-JTSKRJEESA-N 0.000 claims 1
- KIYDUPCDBVIBLR-MBSDFSHPSA-N 3-[[(5s,7s)-3-(2-ethoxy-2-methylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)OCC)C[C@]11C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1 KIYDUPCDBVIBLR-MBSDFSHPSA-N 0.000 claims 1
- NIGGUOAPXRBMQX-JTSKRJEESA-N 3-[[(5s,7s)-3-(2-methoxy-2-methylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)OC)C[C@]11C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1 NIGGUOAPXRBMQX-JTSKRJEESA-N 0.000 claims 1
- QMAMKQFNXOPIMF-CYFREDJKSA-N 3-[[(5s,7s)-3-(3-ethoxy-2,2-dimethylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)COCC)C[C@]11C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1 QMAMKQFNXOPIMF-CYFREDJKSA-N 0.000 claims 1
- LLKGWUPGDQQSHA-MBSDFSHPSA-N 3-[[(5s,7s)-3-(3-methoxy-2,2-dimethylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)COC)C[C@]11C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1 LLKGWUPGDQQSHA-MBSDFSHPSA-N 0.000 claims 1
- INUOLCTVTASXHK-CVDCTZTESA-N 3-[[(5s,7s)-3-(cyclopentylmethyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(OC2=O)C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC1)N2CC1CCCC1 INUOLCTVTASXHK-CVDCTZTESA-N 0.000 claims 1
- JTVPQXIQANZPEW-SGCMCVRUSA-N 3-[[(5s,7s)-3-(oxan-2-ylmethyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(OC2=O)C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC1)N2CC1CCCCO1 JTVPQXIQANZPEW-SGCMCVRUSA-N 0.000 claims 1
- HDVMHTXCOPGAAO-CYFREDJKSA-N 3-[[(5s,7s)-3-[(1-ethylcyclobutyl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O([C@@]1(C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1)C1)C(=O)N1CC1(CC)CCC1 HDVMHTXCOPGAAO-CYFREDJKSA-N 0.000 claims 1
- BPOPBMQXMMAWEW-MBSDFSHPSA-N 3-[[(5s,7s)-3-[(1-methylcyclobutyl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O([C@@]1(C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1)C1)C(=O)N1CC1(C)CCC1 BPOPBMQXMMAWEW-MBSDFSHPSA-N 0.000 claims 1
- AAQGZVFDWFSIHL-WXRCJJMSSA-N 3-[[(5s,7s)-3-[(2-ethyloxan-2-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O([C@@]1(C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1)C1)C(=O)N1CC1(CC)CCCCO1 AAQGZVFDWFSIHL-WXRCJJMSSA-N 0.000 claims 1
- PYSUECLWTZRWBA-IUFWLTQMSA-N 3-[[(5s,7s)-3-[(2-ethyloxolan-2-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O([C@@]1(C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1)C1)C(=O)N1CC1(CC)CCCO1 PYSUECLWTZRWBA-IUFWLTQMSA-N 0.000 claims 1
- WCKHDHJYVRNYDT-IUFWLTQMSA-N 3-[[(5s,7s)-3-[(2-methyloxan-2-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O([C@@]1(C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1)C1)C(=O)N1CC1(C)CCCCO1 WCKHDHJYVRNYDT-IUFWLTQMSA-N 0.000 claims 1
- KXAYEVRKKUTVBD-DGCGVQPYSA-N 3-[[(5s,7s)-3-[(2-methyloxolan-2-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O([C@@]1(C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1)C1)C(=O)N1CC1(C)CCCO1 KXAYEVRKKUTVBD-DGCGVQPYSA-N 0.000 claims 1
- RXQHZTFYGWQLIQ-ZJBJCVSYSA-N 3-[[(5s,7s)-3-[(2s)-2-methylbutyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(C[C@@H](C)CC)C[C@]11C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1 RXQHZTFYGWQLIQ-ZJBJCVSYSA-N 0.000 claims 1
- PSWCGFJVDHOBMJ-JTSKRJEESA-N 3-[[(5s,7s)-3-[2,2-dimethyl-3-(trifluoromethoxy)propyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(COC(F)(F)F)C)C[C@]11C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1 PSWCGFJVDHOBMJ-JTSKRJEESA-N 0.000 claims 1
- BMQIPYWCTFXIKA-CPJSRVTESA-N 3-[[(5s,7s)-3-[[1-(methoxymethyl)cyclopentyl]methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O([C@@]1(C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1)C1)C(=O)N1CC1(COC)CCCC1 BMQIPYWCTFXIKA-CPJSRVTESA-N 0.000 claims 1
- XJZWCXZUKJZTSZ-CPJSRVTESA-N 3-[[(5s,7s)-3-[[4-(methoxymethyl)oxan-4-yl]methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O([C@@]1(C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1)C1)C(=O)N1CC1(COC)CCOCC1 XJZWCXZUKJZTSZ-CPJSRVTESA-N 0.000 claims 1
- ZRBUUFIPVPEXIJ-TZYHBYERSA-N 3-[[(5s,7s)-7-methyl-2-oxo-3-[[(2s)-oxolan-2-yl]methyl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(CCC[C@@](C1)(CN1C2=CC(=CC=C2N=C1)C#N)C)OC1=O)N1C[C@@H]1CCCO1 ZRBUUFIPVPEXIJ-TZYHBYERSA-N 0.000 claims 1
- FNPBGWBZQUJWJH-UHFFFAOYSA-N 3-[[3-(2,2-dimethylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]-6-fluorobenzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)C)CC11CC(CN2C3=CC(=C(F)C=C3N=C2)C#N)CCC1 FNPBGWBZQUJWJH-UHFFFAOYSA-N 0.000 claims 1
- UURWNXDAHMCONL-UHFFFAOYSA-N 3-[[3-(2,2-dimethylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]-7-fluorobenzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)C)CC11CC(CN2C3=CC(=CC(F)=C3N=C2)C#N)CCC1 UURWNXDAHMCONL-UHFFFAOYSA-N 0.000 claims 1
- IBIVABPEKTVFJU-UHFFFAOYSA-N 3-[[3-(2,2-dimethylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]-7-methoxybenzimidazole-5-carbonitrile Chemical compound C1=NC=2C(OC)=CC(C#N)=CC=2N1CC(C1)CCCC21CN(CC(C)(C)C)C(=O)O2 IBIVABPEKTVFJU-UHFFFAOYSA-N 0.000 claims 1
- QMZFTVIOZWPQJS-UHFFFAOYSA-N 3-[[3-(2,2-dimethylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]-7-methylbenzimidazole-5-carbonitrile Chemical compound C1=NC=2C(C)=CC(C#N)=CC=2N1CC(C1)CCCC21CN(CC(C)(C)C)C(=O)O2 QMZFTVIOZWPQJS-UHFFFAOYSA-N 0.000 claims 1
- SWQFFJVGEHZGRF-UHFFFAOYSA-N 3-[[3-(2,2-dimethylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)C)CC11CC(CN2C3=CC(=CC=C3N=C2)C#N)CCC1 SWQFFJVGEHZGRF-UHFFFAOYSA-N 0.000 claims 1
- IKJPHZIPUNIZRT-UHFFFAOYSA-N 3-[[3-(2,2-dimethylpropyl)-7-ethyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1C(CC)(CN2C3=CC(=CC=C3N=C2)C#N)CCCC21CN(CC(C)(C)C)C(=O)O2 IKJPHZIPUNIZRT-UHFFFAOYSA-N 0.000 claims 1
- FCBLQUVTQLNDPM-UHFFFAOYSA-N 3-[[3-(2,2-dimethylpropyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]-2-ethylbenzimidazole-5-carbonitrile Chemical compound CCC1=NC2=CC=C(C#N)C=C2N1CC(C1)(C)CCCC21CN(CC(C)(C)C)C(=O)O2 FCBLQUVTQLNDPM-UHFFFAOYSA-N 0.000 claims 1
- RXQHZTFYGWQLIQ-UHFFFAOYSA-N 3-[[3-(2-methylbutyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)CC)CC11CC(CN2C3=CC(=CC=C3N=C2)C#N)CCC1 RXQHZTFYGWQLIQ-UHFFFAOYSA-N 0.000 claims 1
- NMEONZUVYFLYMZ-UHFFFAOYSA-N 3-[[3-[(4-ethyloxan-4-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1C2(CC(CN3C4=CC(=CC=C4N=C3)C#N)CCC2)OC(=O)N1CC1(CC)CCOCC1 NMEONZUVYFLYMZ-UHFFFAOYSA-N 0.000 claims 1
- NICYTXJGZRYCEQ-UHFFFAOYSA-N 3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2N=CNC2=C1 NICYTXJGZRYCEQ-UHFFFAOYSA-N 0.000 claims 1
- NPSZPVALEHTUKD-UHFFFAOYSA-N 6-chloro-3-[[3-(2,2-dimethylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)C)CC11CC(CN2C3=CC(=C(Cl)C=C3N=C2)C#N)CCC1 NPSZPVALEHTUKD-UHFFFAOYSA-N 0.000 claims 1
- DQLZXZOGEYXMHQ-UHFFFAOYSA-N 6-fluoro-3-[[2-oxo-3-(2,2,3,3,3-pentafluoropropyl)-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1=2C=C(C#N)C(F)=CC=2N=CN1CC(C1)CCCC21CN(CC(F)(F)C(F)(F)F)C(=O)O2 DQLZXZOGEYXMHQ-UHFFFAOYSA-N 0.000 claims 1
- JUOQIFQLZWSETR-UHFFFAOYSA-N 6-fluoro-3-[[3-(3-methoxy-2,2-dimethylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)COC)CC11CC(CN2C3=CC(=C(F)C=C3N=C2)C#N)CCC1 JUOQIFQLZWSETR-UHFFFAOYSA-N 0.000 claims 1
- IZQIRJFRVOUSEN-UHFFFAOYSA-N 6-fluoro-3-[[3-[(2-methyloxolan-2-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1C2(CC(CN3C4=CC(=C(F)C=C4N=C3)C#N)CCC2)OC(=O)N1CC1(C)CCCO1 IZQIRJFRVOUSEN-UHFFFAOYSA-N 0.000 claims 1
- OGJZZAIEOUBHSH-UHFFFAOYSA-N 6-fluoro-3-[[3-[[1-(methoxymethyl)cyclopropyl]methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C1C2(CC(CN3C4=CC(=C(F)C=C4N=C3)C#N)CCC2)OC(=O)N1CC1(COC)CC1 OGJZZAIEOUBHSH-UHFFFAOYSA-N 0.000 claims 1
- HYCFPOGWCDSNIN-UHFFFAOYSA-N 7-[(5,6-dichlorobenzimidazol-1-yl)methyl]-3-(2,2-dimethylpropyl)-7-methyl-1-oxa-3-azaspiro[4.5]decan-2-one Chemical compound O1C(=O)N(CC(C)(C)C)CC11CC(C)(CN2C3=CC(Cl)=C(Cl)C=C3N=C2)CCC1 HYCFPOGWCDSNIN-UHFFFAOYSA-N 0.000 claims 1
- GNLAAXCBFXVBKS-UHFFFAOYSA-N 7-[(5,6-difluorobenzimidazol-1-yl)methyl]-3-(2,2-dimethylpropyl)-7-methyl-1-oxa-3-azaspiro[4.5]decan-2-one Chemical compound O1C(=O)N(CC(C)(C)C)CC11CC(C)(CN2C3=CC(F)=C(F)C=C3N=C2)CCC1 GNLAAXCBFXVBKS-UHFFFAOYSA-N 0.000 claims 1
- QWCWRSQLWAOGMW-UHFFFAOYSA-N 7-[(5,6-dimethoxybenzimidazol-1-yl)methyl]-3-(2,2-dimethylpropyl)-7-methyl-1-oxa-3-azaspiro[4.5]decan-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2N=CN1CC(C1)(C)CCCC21CN(CC(C)(C)C)C(=O)O2 QWCWRSQLWAOGMW-UHFFFAOYSA-N 0.000 claims 1
- PNJBTWJVOGYBFR-UHFFFAOYSA-N 7-[(5,6-dimethylbenzimidazol-1-yl)methyl]-3-(2,2-dimethylpropyl)-7-methyl-1-oxa-3-azaspiro[4.5]decan-2-one Chemical compound C1=2C=C(C)C(C)=CC=2N=CN1CC(C1)(C)CCCC21CN(CC(C)(C)C)C(=O)O2 PNJBTWJVOGYBFR-UHFFFAOYSA-N 0.000 claims 1
- OCCOJWYXYDCXCX-UHFFFAOYSA-N 7-[(6-chloro-5-fluorobenzimidazol-1-yl)methyl]-3-[(2-methyloxolan-2-yl)methyl]-1-oxa-3-azaspiro[4.5]decan-2-one Chemical compound C1C2(CC(CN3C4=CC(Cl)=C(F)C=C4N=C3)CCC2)OC(=O)N1CC1(C)CCCO1 OCCOJWYXYDCXCX-UHFFFAOYSA-N 0.000 claims 1
- YTCPSYKCXMZNQP-UHFFFAOYSA-N 7-[(6-chlorobenzimidazol-1-yl)methyl]-3-(2,2-dimethylpropyl)-7-methyl-1-oxa-3-azaspiro[4.5]decan-2-one Chemical compound O1C(=O)N(CC(C)(C)C)CC11CC(C)(CN2C3=CC(Cl)=CC=C3N=C2)CCC1 YTCPSYKCXMZNQP-UHFFFAOYSA-N 0.000 claims 1
- ACCLBMKXVLYIEH-UHFFFAOYSA-N 7-bromo-3-[[3-(2,2-dimethylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)C)CC11CC(CN2C3=CC(=CC(Br)=C3N=C2)C#N)CCC1 ACCLBMKXVLYIEH-UHFFFAOYSA-N 0.000 claims 1
- MTZIRQFFNLGAER-YHEJKZAPSA-N 7-chloro-3-[[(5s,7s)-2-oxo-3-[[(2s)-oxolan-2-yl]methyl]-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@]1(CCC[C@@H](C1)CN1C=2C=C(C=C(C=2N=C1)Cl)C#N)OC1=O)N1C[C@@H]1CCCO1 MTZIRQFFNLGAER-YHEJKZAPSA-N 0.000 claims 1
- ATRNWCCZUXGMOZ-NYHFZMIOSA-N 7-chloro-3-[[(5s,7s)-3-(2,2-dimethylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)C)C[C@]11C[C@@H](CN2C3=CC(=CC(Cl)=C3N=C2)C#N)CCC1 ATRNWCCZUXGMOZ-NYHFZMIOSA-N 0.000 claims 1
- VSZYLDNPRSGSDF-GDTQQENISA-N 7-chloro-3-[[(5s,7s)-3-[(2-methyloxolan-2-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O([C@@]1(C[C@@H](CN2C3=CC(=CC(Cl)=C3N=C2)C#N)CCC1)C1)C(=O)N1CC1(C)CCCO1 VSZYLDNPRSGSDF-GDTQQENISA-N 0.000 claims 1
- NBPGMHBTNZIKNT-UHFFFAOYSA-N 7-chloro-3-[[3-(2,2-dimethylpropyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)C)CC11CC(C)(CN2C3=CC(=CC(Cl)=C3N=C2)C#N)CCC1 NBPGMHBTNZIKNT-UHFFFAOYSA-N 0.000 claims 1
- 206010007559 Cardiac failure congestive Diseases 0.000 claims 1
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- 206010019280 Heart failures Diseases 0.000 claims 1
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- 208000009722 Overactive Urinary Bladder Diseases 0.000 claims 1
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- 239000003937 drug carrier Substances 0.000 claims 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 1
- 208000005264 motor neuron disease Diseases 0.000 claims 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 201000008482 osteoarthritis Diseases 0.000 claims 1
- 208000020629 overactive bladder Diseases 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161498099P | 2011-06-17 | 2011-06-17 | |
| US61/498,099 | 2011-06-17 | ||
| PCT/US2012/042603 WO2012174340A1 (en) | 2011-06-17 | 2012-06-15 | Trpv4 antagonists |
Publications (3)
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| JP2014520118A JP2014520118A (ja) | 2014-08-21 |
| JP2014520118A5 true JP2014520118A5 (enExample) | 2015-07-16 |
| JP5969015B2 JP5969015B2 (ja) | 2016-08-10 |
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| EP (1) | EP2720697B1 (enExample) |
| JP (1) | JP5969015B2 (enExample) |
| ES (1) | ES2595606T3 (enExample) |
| WO (1) | WO2012174340A1 (enExample) |
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| JO3154B1 (ar) * | 2011-06-17 | 2017-09-20 | Glaxosmithkline Llc | عوامل مضادة لـ trpv4 |
| US9487507B2 (en) | 2011-06-17 | 2016-11-08 | Glaxosmithkline Intellectual Property (No. 2) Limited | TRPV4 antagonists |
| US9499533B2 (en) | 2012-03-27 | 2016-11-22 | Shionogi & Co., Ltd. | Aromatic 5-membered heterocyclic derivative having TRPV4-Inhibiting activity |
| WO2015046193A1 (ja) | 2013-09-25 | 2015-04-02 | 塩野義製薬株式会社 | Ｔｒｐｖ４阻害活性を有する芳香族複素環式アミン誘導体 |
| ES2813108T3 (es) * | 2016-05-19 | 2021-03-22 | Glaxosmithkline Ip No 2 Ltd | Antagonista de TRPV4 |
| US10968209B2 (en) | 2016-05-19 | 2021-04-06 | Glaxosmithkline Intellectual Property (No.2) Limited | TRPV4 antagonist |
| WO2018185701A1 (en) * | 2017-04-06 | 2018-10-11 | Glaxosmithkline Intellectual Property (No.2) Limited | Trpv4 antagonists as antitussive agents |
| JP7692219B2 (ja) | 2020-04-30 | 2025-06-13 | ラクオリア創薬株式会社 | Ｔｒｐｖ４拮抗薬としてのピリミジン－４（３ｈ）－オン誘導体 |
| EP4183415A4 (en) | 2020-07-16 | 2024-07-17 | RaQualia Pharma Inc. | Trpv4 inhibitor as therapeutic drug for eye disease |
| EP4551572A1 (en) | 2022-07-08 | 2025-05-14 | Actio Biosciences, Inc. | Therapeutic compounds and methods |
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| ATE482945T1 (de) | 1998-05-26 | 2010-10-15 | Chugai Pharmaceutical Co Ltd | Heterozyklische indolderivate und mono- oder diazaindol-derivate |
| EP1187610A2 (en) | 1999-05-12 | 2002-03-20 | Neurosearch A/S | Use of ion channel modulating agents |
| CA2531619A1 (en) * | 2003-07-16 | 2005-01-27 | Neurogen Corporation | Biaryl piperazinyl-pyridine analogues |
| TW200819457A (en) * | 2006-08-30 | 2008-05-01 | Actelion Pharmaceuticals Ltd | Spiro antibiotic derivatives |
| US20090042897A1 (en) | 2007-02-01 | 2009-02-12 | Glaxo Group Limited | Chemical Compounds |
| GB0707934D0 (en) | 2007-04-24 | 2007-05-30 | Glaxo Group Ltd | Chemical compounds |
| MX2010001486A (es) * | 2007-08-09 | 2010-03-01 | Abbott Lab | Derivados de tetrahidropiridin carboxamida como antagonistas de trpvl. |
| TW200944520A (en) * | 2008-01-29 | 2009-11-01 | Glaxo Group Ltd | Spiro compounds as NPY Y5 receptor antagonists |
| US8450484B2 (en) * | 2008-07-25 | 2013-05-28 | GlaxoSmithKline, LLC | TRPV4 antagonists |
| JP2012006837A (ja) * | 2008-09-30 | 2012-01-12 | Mochida Pharmaceut Co Ltd | ２−インドールアクリルアミド類縁体 |
| JO3154B1 (ar) | 2011-06-17 | 2017-09-20 | Glaxosmithkline Llc | عوامل مضادة لـ trpv4 |
| US9487507B2 (en) * | 2011-06-17 | 2016-11-08 | Glaxosmithkline Intellectual Property (No. 2) Limited | TRPV4 antagonists |
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2012
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- 2012-06-15 JP JP2014516015A patent/JP5969015B2/ja not_active Expired - Fee Related
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- 2012-06-15 WO PCT/US2012/042603 patent/WO2012174340A1/en not_active Ceased
- 2012-06-15 EP EP12801296.0A patent/EP2720697B1/en active Active
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