ES2595606T3 - Antagonistas TRPV4 - Google Patents

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Publication number

ES2595606T3

ES2595606T3 ES12801296.0T ES12801296T ES2595606T3 ES 2595606 T3 ES2595606 T3 ES 2595606T3 ES 12801296 T ES12801296 T ES 12801296T ES 2595606 T3 ES2595606 T3 ES 2595606T3

Authority

ES

Spain

Prior art keywords

methyl

oxa

alkyl

azaspiro

decan

Prior art date

2011-06-17

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.)

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• 101150098315 TRPV4 gene Proteins 0.000 title description 38
• 102000003567 TRPV4 Human genes 0.000 title description 37
• 239000005557 antagonist Substances 0.000 title description 11
• 150000001875 compounds Chemical class 0.000 claims abstract description 139
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 81
• -1 C1-2alkyl Chemical group 0.000 claims abstract description 70
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 63
• 239000001257 hydrogen Substances 0.000 claims abstract description 63
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 59
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 55
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 40
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 36
• 150000002431 hydrogen Chemical group 0.000 claims abstract description 32
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 25
• 229910052701 rubidium Inorganic materials 0.000 claims abstract description 24
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims abstract description 24
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims abstract description 24
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 22
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 22
• 150000003839 salts Chemical class 0.000 claims abstract description 22
• 125000001424 substituent group Chemical group 0.000 claims abstract description 22
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 20
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 20
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 12
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 11
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims abstract description 8
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 8
• 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 8
• 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 8
• 125000003554 tetrahydropyrrolyl group Chemical group 0.000 claims abstract description 8
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 7
• 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims abstract description 7
• 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims abstract description 6
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical group O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims abstract description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 3
• 125000005843 halogen group Chemical group 0.000 claims abstract 16
• WSGPLSDARZNMCW-FCVLBCLDSA-N methyl (1s,4as,5s,7as)-5-hydroxy-7-(hydroxymethyl)-1-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-4-carboxylate Chemical compound O([C@@H]1OC=C([C@@H]2[C@H]1C(=C[C@@H]2O)CO)C(=O)OC)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O WSGPLSDARZNMCW-FCVLBCLDSA-N 0.000 claims abstract 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 21
• LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims description 20
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
• 239000008194 pharmaceutical composition Substances 0.000 claims description 15
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
• 208000035475 disorder Diseases 0.000 claims description 12
• 206010030113 Oedema Diseases 0.000 claims description 9
• 208000002193 Pain Diseases 0.000 claims description 9
• 206010019280 Heart failures Diseases 0.000 claims description 8
• 230000002265 prevention Effects 0.000 claims description 8
• 206010037423 Pulmonary oedema Diseases 0.000 claims description 7
• AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 claims description 7
• 208000005333 pulmonary edema Diseases 0.000 claims description 7
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 6
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 6
• ZAJNGDIORYACQU-UHFFFAOYSA-N decan-2-one Chemical compound CCCCCCCCC(C)=O ZAJNGDIORYACQU-UHFFFAOYSA-N 0.000 claims description 6
• 230000000968 intestinal effect Effects 0.000 claims description 6
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 6
• 125000006217 methyl sulfide group Chemical group [H]C([H])([H])S* 0.000 claims description 6
• 201000008482 osteoarthritis Diseases 0.000 claims description 6
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 5
• 206010020853 Hypertonic bladder Diseases 0.000 claims description 5
• 206010061218 Inflammation Diseases 0.000 claims description 5
• 208000004852 Lung Injury Diseases 0.000 claims description 5
• 208000009722 Overactive Urinary Bladder Diseases 0.000 claims description 5
• 206010069363 Traumatic lung injury Diseases 0.000 claims description 5
• 206010069351 acute lung injury Diseases 0.000 claims description 5
• 208000006673 asthma Diseases 0.000 claims description 5
• 210000000988 bone and bone Anatomy 0.000 claims description 5
• 230000002068 genetic effect Effects 0.000 claims description 5
• 230000004054 inflammatory process Effects 0.000 claims description 5
• 231100000515 lung injury Toxicity 0.000 claims description 5
• 208000020629 overactive bladder Diseases 0.000 claims description 5
• 201000009890 sinusitis Diseases 0.000 claims description 5
• 230000009885 systemic effect Effects 0.000 claims description 5
• 201000001320 Atherosclerosis Diseases 0.000 claims description 4
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
• 206010016807 Fluid retention Diseases 0.000 claims description 4
• 206010058061 Gastrointestinal oedema Diseases 0.000 claims description 4
• 206010020772 Hypertension Diseases 0.000 claims description 4
• 208000019693 Lung disease Diseases 0.000 claims description 4
• 208000001647 Renal Insufficiency Diseases 0.000 claims description 4
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 4
• 206010040047 Sepsis Diseases 0.000 claims description 4
• 230000003187 abdominal effect Effects 0.000 claims description 4
• 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 4
• 201000006370 kidney failure Diseases 0.000 claims description 4
• 208000005264 motor neuron disease Diseases 0.000 claims description 4
• 208000005069 pulmonary fibrosis Diseases 0.000 claims description 4
• 206010039083 rhinitis Diseases 0.000 claims description 4
• 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 description 3
• HYUHFAWUOGCJHB-ALVJRTDLSA-N 3-[[(5s,7s)-3-(2,2-dimethylcyclohexyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound CC1(C)CCCCC1N1C(=O)O[C@@]2(C[C@@H](CN3C4=CC(=CC=C4N=C3)C#N)CCC2)C1 HYUHFAWUOGCJHB-ALVJRTDLSA-N 0.000 claims description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 208000015943 Coeliac disease Diseases 0.000 claims description 3
• 206010010774 Constipation Diseases 0.000 claims description 3
• 208000011231 Crohn disease Diseases 0.000 claims description 3
• 206010012735 Diarrhoea Diseases 0.000 claims description 3
• 208000034347 Faecal incontinence Diseases 0.000 claims description 3
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
• 208000007101 Muscle Cramp Diseases 0.000 claims description 3
• 206010009887 colitis Diseases 0.000 claims description 3
• 206010016766 flatulence Diseases 0.000 claims description 3
• 230000035874 hyperreactivity Effects 0.000 claims description 3
• 239000008101 lactose Substances 0.000 claims description 3
• HMSPOIKRPKEGGE-UHFFFAOYSA-N methyl 3-[7-[(6-cyanobenzimidazol-1-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]decan-3-yl]-2,2-dimethylpropanoate Chemical compound O1C(=O)N(CC(C)(C)C(=O)OC)CC11CC(CN2C3=CC(=CC=C3N=C2)C#N)CCC1 HMSPOIKRPKEGGE-UHFFFAOYSA-N 0.000 claims description 3
• 238000002560 therapeutic procedure Methods 0.000 claims description 3
• 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 description 2
• 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 description 2
• LFEFNSUDXFICTD-MBSDFSHPSA-N 3-[[(5s,7s)-3-(2,2-dimethylbutyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound O1C(=O)N(CC(C)(C)CC)C[C@]11C[C@@H](CN2C3=CC(=CC=C3N=C2)C#N)CCC1 LFEFNSUDXFICTD-MBSDFSHPSA-N 0.000 claims description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• SGRYIBCCPMHPRD-VXKWHMMOSA-N 3-[[(5s,7s)-7-methyl-3-(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[C@]11C[C@@](C)(CN2C3=CC(=CC=C3N=C2)C#N)CCC1 SGRYIBCCPMHPRD-VXKWHMMOSA-N 0.000 claims description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 230000004064 dysfunction Effects 0.000 claims description 2
• 210000002161 motor neuron Anatomy 0.000 claims description 2
• SWQFFJVGEHZGRF-MTIPOKABSA-N 2,7-dideuterio-3-[[(5s,7s)-3-(2,2-dimethylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound C([C@@H](C1)CN2C3=CC(=CC([2H])=C3N=C2[2H])C#N)CC[C@]21CN(CC(C)(C)C)C(=O)O2 SWQFFJVGEHZGRF-MTIPOKABSA-N 0.000 claims 1
• SWQFFJVGEHZGRF-XPEWCTJMSA-N 2,7-dideuterio-3-[[3-(2,2-dimethylpropyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl]methyl]benzimidazole-5-carbonitrile Chemical compound [2H]C1=NC2=C([2H])C=C(C#N)C=C2N1CC(C1)CCCC21CN(CC(C)(C)C)C(=O)O2 SWQFFJVGEHZGRF-XPEWCTJMSA-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
• 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
• 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
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