NO313237B1 - Nye substituerte piperidiner som er anvendbare for behandling av allergiske sykdommer og farmasöytisk preparat - Google Patents
Nye substituerte piperidiner som er anvendbare for behandling av allergiske sykdommer og farmasöytisk preparat Download PDFInfo
- Publication number
- NO313237B1 NO313237B1 NO19970831A NO970831A NO313237B1 NO 313237 B1 NO313237 B1 NO 313237B1 NO 19970831 A NO19970831 A NO 19970831A NO 970831 A NO970831 A NO 970831A NO 313237 B1 NO313237 B1 NO 313237B1
- Authority
- NO
- Norway
- Prior art keywords
- ethyl
- trimethoxybenzoyl
- pyrrolidine
- carbonyl
- mixture
- Prior art date
Links
- 208000026935 allergic disease Diseases 0.000 title claims abstract description 4
- 238000011282 treatment Methods 0.000 title claims abstract description 4
- 239000000825 pharmaceutical preparation Substances 0.000 title claims 2
- 150000003053 piperidines Chemical class 0.000 title abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- 150000001875 compounds Chemical class 0.000 claims description 368
- 238000006243 chemical reaction Methods 0.000 claims description 202
- 238000000034 method Methods 0.000 claims description 200
- 239000000203 mixture Substances 0.000 claims description 131
- -1 methylenedioxy Chemical group 0.000 claims description 58
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 41
- 239000001257 hydrogen Substances 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 238000010511 deprotection reaction Methods 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 17
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 17
- 229910052794 bromium Inorganic materials 0.000 claims description 17
- 239000000460 chlorine Substances 0.000 claims description 16
- 229910052801 chlorine Inorganic materials 0.000 claims description 16
- WJEAYMAHIVBPGF-UHFFFAOYSA-N [1-[2-[3-(3,4-dichlorophenyl)-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCN3CCC(CC3)C(=O)C=3N(C4=CC=CC=C4N=3)CC=3C=CC(F)=CC=3)(CC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 WJEAYMAHIVBPGF-UHFFFAOYSA-N 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 239000012279 sodium borohydride Substances 0.000 claims description 11
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 11
- XHIAYAAKBSHSOX-UHFFFAOYSA-N 1h-benzimidazol-2-yl-[1-[2-[3-phenyl-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCN3CCC(CC3)C(=O)C=3NC4=CC=CC=C4N=3)(CC2)C=2C=CC=CC=2)=C1 XHIAYAAKBSHSOX-UHFFFAOYSA-N 0.000 claims description 10
- ADZSGFZICHOKOJ-UHFFFAOYSA-N [1-(2-ethoxyethyl)benzimidazol-2-yl]-[1-[2-[3-phenyl-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]methanone Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1C(=O)C(CC1)CCN1CCC(C1)(C=2C=CC=CC=2)CCN1C(=O)C1=CC(OC)=C(OC)C(OC)=C1 ADZSGFZICHOKOJ-UHFFFAOYSA-N 0.000 claims description 7
- IPQSEKMUUNQIQD-UHFFFAOYSA-N [1-[2-[3-(3,4-dimethoxyphenyl)-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]methanone Chemical compound C1=C(OC)C(OC)=CC=C1C1(CCN2CCC(CC2)C(=O)C=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CN(C(=O)C=2C=C(OC)C(OC)=C(OC)C=2)CC1 IPQSEKMUUNQIQD-UHFFFAOYSA-N 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- USQNYIPSWUNBEC-UHFFFAOYSA-N [1-[2-[3-(1,3-benzodioxol-5-yl)-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCN3CCC(CC3)C(=O)C=3N(C4=CC=CC=C4N=3)CC=3C=CC(F)=CC=3)(CC2)C=2C=C3OCOC3=CC=2)=C1 USQNYIPSWUNBEC-UHFFFAOYSA-N 0.000 claims description 6
- 239000003638 chemical reducing agent Substances 0.000 claims description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 6
- JGCCIXQSCXPPCX-UHFFFAOYSA-N 1,3-dibenzyl-3-[2-[4-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]-4-hydroxypiperidin-1-yl]ethyl]pyrrolidin-2-one Chemical compound C1CC(O)(C=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CCN1CCC1(C(N(CC=2C=CC=CC=2)CC1)=O)CC1=CC=CC=C1 JGCCIXQSCXPPCX-UHFFFAOYSA-N 0.000 claims description 5
- GHVPKFCDNOFWEW-UHFFFAOYSA-N 1-[3-(1,3-benzodioxol-5-yl)-3-[2-[4-[1-[(4-fluorophenyl)methyl]benzimidazole-2-carbonyl]piperidin-1-yl]ethyl]pyrrolidin-1-yl]-2-(3-propan-2-yloxyphenyl)ethanone Chemical compound CC(C)OC1=CC=CC(CC(=O)N2CC(CCN3CCC(CC3)C(=O)C=3N(C4=CC=CC=C4N=3)CC=3C=CC(F)=CC=3)(CC2)C=2C=C3OCOC3=CC=2)=C1 GHVPKFCDNOFWEW-UHFFFAOYSA-N 0.000 claims description 5
- BSVGNAQMDXJFNE-UHFFFAOYSA-N 1h-benzimidazol-2-yl-[1-[2-[3-(3,4-dichlorophenyl)-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCN3CCC(CC3)C(=O)C=3NC4=CC=CC=C4N=3)(CC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 BSVGNAQMDXJFNE-UHFFFAOYSA-N 0.000 claims description 5
- JFTVUEGYWJVTCA-UHFFFAOYSA-N 3-[(3,4-dichlorophenyl)methyl]-3-[2-[4-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]-4-hydroxypiperidin-1-yl]ethyl]-1-[(3,4,5-trimethoxyphenyl)methyl]pyrrolidin-2-one Chemical compound COC1=C(OC)C(OC)=CC(CN2C(C(CCN3CCC(O)(CC3)C=3N(C4=CC=CC=C4N=3)CC=3C=CC(F)=CC=3)(CC=3C=C(Cl)C(Cl)=CC=3)CC2)=O)=C1 JFTVUEGYWJVTCA-UHFFFAOYSA-N 0.000 claims description 5
- VDAMCZUHIJCJPK-UHFFFAOYSA-N [1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]-[1-[2-[3-phenyl-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCN3CCC(CC3)C(=O)C=3N(C4=CC=CC=C4N=3)CC=3C=CC(F)=CC=3)(CC2)C=2C=CC=CC=2)=C1 VDAMCZUHIJCJPK-UHFFFAOYSA-N 0.000 claims description 5
- QPFYLKDZMPQIPZ-UHFFFAOYSA-N [1-[2-[3-(1,3-benzodioxol-5-yl)-1-(2,4-dichlorobenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]methanone Chemical compound C1=CC(F)=CC=C1CN1C2=CC=CC=C2N=C1C(=O)C1CCN(CCC2(CN(CC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)C=2C=C3OCOC3=CC=2)CC1 QPFYLKDZMPQIPZ-UHFFFAOYSA-N 0.000 claims description 5
- ORBDOXUKPRMJQT-UHFFFAOYSA-N [1-[2-[3-(3,4-dichlorophenyl)-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]-[1-(2-morpholin-4-ylethyl)benzimidazol-2-yl]methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCN3CCC(CC3)C(=O)C=3N(C4=CC=CC=C4N=3)CCN3CCOCC3)(CC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 ORBDOXUKPRMJQT-UHFFFAOYSA-N 0.000 claims description 5
- VBMKWPABKWXAOB-UHFFFAOYSA-N [1-[2-[3-(3,4-dichlorophenyl)-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]-[1-(pyridin-2-ylmethyl)benzimidazol-2-yl]methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCN3CCC(CC3)C(=O)C=3N(C4=CC=CC=C4N=3)CC=3N=CC=CC=3)(CC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 VBMKWPABKWXAOB-UHFFFAOYSA-N 0.000 claims description 5
- WVQQYRWWDMHAOE-UHFFFAOYSA-N [3-(3,4-dichlorophenyl)-3-[2-[4-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]-4-hydroxypiperidin-1-yl]ethyl]pyrrolidin-1-yl]-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCN3CCC(O)(CC3)C=3N(C4=CC=CC=C4N=3)CC=3C=CC(F)=CC=3)(CC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 WVQQYRWWDMHAOE-UHFFFAOYSA-N 0.000 claims description 5
- FHQIZZULOZUTPI-UHFFFAOYSA-N [3-(3,4-dimethoxyphenyl)-3-[2-[4-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]-4-hydroxypiperidin-1-yl]ethyl]pyrrolidin-1-yl]-(3,4,5-trimethoxyphenyl)methanone Chemical compound C1=C(OC)C(OC)=CC=C1C1(CCN2CCC(O)(CC2)C=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CN(C(=O)C=2C=C(OC)C(OC)=C(OC)C=2)CC1 FHQIZZULOZUTPI-UHFFFAOYSA-N 0.000 claims description 5
- CUKBOHPSSFJJFQ-UHFFFAOYSA-N ethyl 4-[2-[1-[2-[3-(3,4-dichlorophenyl)-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidine-4-carbonyl]benzimidazol-1-yl]butanoate Chemical compound N=1C2=CC=CC=C2N(CCCC(=O)OCC)C=1C(=O)C(CC1)CCN1CCC(C1)(C=2C=C(Cl)C(Cl)=CC=2)CCN1C(=O)C1=CC(OC)=C(OC)C(OC)=C1 CUKBOHPSSFJJFQ-UHFFFAOYSA-N 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 5
- ZFPPUHTZTYNOKP-UHFFFAOYSA-N methyl 2-[3-[2-[1-[2-[3-phenyl-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidine-4-carbonyl]benzimidazol-1-yl]propoxy]benzoate Chemical compound COC(=O)C1=CC=CC=C1OCCCN1C2=CC=CC=C2N=C1C(=O)C1CCN(CCC2(CN(CC2)C(=O)C=2C=C(OC)C(OC)=C(OC)C=2)C=2C=CC=CC=2)CC1 ZFPPUHTZTYNOKP-UHFFFAOYSA-N 0.000 claims description 5
- RBJZEZVXAVEQFQ-UHFFFAOYSA-N methyl 4-[[2-[1-[2-[3-(3,4-dimethoxyphenyl)-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidine-4-carbonyl]benzimidazol-1-yl]methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CN1C2=CC=CC=C2N=C1C(=O)C1CCN(CCC2(CN(CC2)C(=O)C=2C=C(OC)C(OC)=C(OC)C=2)C=2C=C(OC)C(OC)=CC=2)CC1 RBJZEZVXAVEQFQ-UHFFFAOYSA-N 0.000 claims description 5
- WYLMUYOKAITMJI-UHFFFAOYSA-N methyl 4-[[2-[1-[2-[3-phenyl-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidine-4-carbonyl]benzimidazol-1-yl]methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CN1C2=CC=CC=C2N=C1C(=O)C1CCN(CCC2(CN(CC2)C(=O)C=2C=C(OC)C(OC)=C(OC)C=2)C=2C=CC=CC=2)CC1 WYLMUYOKAITMJI-UHFFFAOYSA-N 0.000 claims description 5
- 238000006268 reductive amination reaction Methods 0.000 claims description 5
- NGNTVUZXGVROKS-UHFFFAOYSA-N 1-[3-(3,4-dichlorophenyl)-3-[2-[4-[1-[(4-fluorophenyl)methyl]benzimidazole-2-carbonyl]piperidin-1-yl]ethyl]piperidin-1-yl]-2-(3-propan-2-yloxyphenyl)ethanone Chemical compound CC(C)OC1=CC=CC(CC(=O)N2CC(CCN3CCC(CC3)C(=O)C=3N(C4=CC=CC=C4N=3)CC=3C=CC(F)=CC=3)(CCC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 NGNTVUZXGVROKS-UHFFFAOYSA-N 0.000 claims description 4
- XMRHEUULHFVWJE-UHFFFAOYSA-N 1h-benzimidazol-2-yl-[1-[2-[3-(3,4-dimethoxyphenyl)-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]methanone Chemical compound C1=C(OC)C(OC)=CC=C1C1(CCN2CCC(CC2)C(=O)C=2NC3=CC=CC=C3N=2)CN(C(=O)C=2C=C(OC)C(OC)=C(OC)C=2)CC1 XMRHEUULHFVWJE-UHFFFAOYSA-N 0.000 claims description 4
- OHIIQHKQTCNQGZ-UHFFFAOYSA-N 3-[(2,4-difluorophenyl)methyl]-3-[2-[4-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]-4-hydroxypiperidin-1-yl]ethyl]-1-[(3,4,5-trimethoxyphenyl)methyl]pyrrolidin-2-one Chemical compound COC1=C(OC)C(OC)=CC(CN2C(C(CCN3CCC(O)(CC3)C=3N(C4=CC=CC=C4N=3)CC=3C=CC(F)=CC=3)(CC=3C(=CC(F)=CC=3)F)CC2)=O)=C1 OHIIQHKQTCNQGZ-UHFFFAOYSA-N 0.000 claims description 4
- QNWOMKIQFUVNRZ-UHFFFAOYSA-N 3-[(4-fluorophenyl)methyl]-3-[2-[4-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]-4-hydroxypiperidin-1-yl]ethyl]-1-[(3,4,5-trimethoxyphenyl)methyl]pyrrolidin-2-one Chemical compound COC1=C(OC)C(OC)=CC(CN2C(C(CCN3CCC(O)(CC3)C=3N(C4=CC=CC=C4N=3)CC=3C=CC(F)=CC=3)(CC=3C=CC(F)=CC=3)CC2)=O)=C1 QNWOMKIQFUVNRZ-UHFFFAOYSA-N 0.000 claims description 4
- ZFTUCIZHPZEYDX-UHFFFAOYSA-N 3-benzyl-3-[2-[4-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]-4-hydroxypiperidin-1-yl]ethyl]-1-[(3,4,5-trimethoxyphenyl)methyl]pyrrolidin-2-one Chemical compound COC1=C(OC)C(OC)=CC(CN2C(C(CCN3CCC(O)(CC3)C=3N(C4=CC=CC=C4N=3)CC=3C=CC(F)=CC=3)(CC=3C=CC=CC=3)CC2)=O)=C1 ZFTUCIZHPZEYDX-UHFFFAOYSA-N 0.000 claims description 4
- BEYBSSSCFNIKNG-UHFFFAOYSA-N [1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]-[1-[2-[3-[4-(trifluoromethyl)phenyl]-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCN3CCC(CC3)C(=O)C=3N(C4=CC=CC=C4N=3)CC=3C=CC(F)=CC=3)(CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 BEYBSSSCFNIKNG-UHFFFAOYSA-N 0.000 claims description 4
- CGNVNXXLENQGRB-UHFFFAOYSA-N [1-[2-(furan-2-ylmethoxy)ethyl]benzimidazol-2-yl]-[1-[2-[3-phenyl-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCN3CCC(CC3)C(=O)C=3N(C4=CC=CC=C4N=3)CCOCC=3OC=CC=3)(CC2)C=2C=CC=CC=2)=C1 CGNVNXXLENQGRB-UHFFFAOYSA-N 0.000 claims description 4
- PVOZTVLKZYEWDB-UHFFFAOYSA-N [1-[2-[3-(2,4-difluorophenyl)-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCN3CCC(CC3)C(=O)C=3N(C4=CC=CC=C4N=3)CC=3C=CC(F)=CC=3)(CC2)C=2C(=CC(F)=CC=2)F)=C1 PVOZTVLKZYEWDB-UHFFFAOYSA-N 0.000 claims description 4
- BUFPSVPHZWUBCB-UHFFFAOYSA-N [1-[2-[3-(3,4-difluorophenyl)-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]-[1-(2-ethoxyethyl)benzimidazol-2-yl]methanone Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1C(=O)C(CC1)CCN1CCC(C1)(C=2C=C(F)C(F)=CC=2)CCN1C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BUFPSVPHZWUBCB-UHFFFAOYSA-N 0.000 claims description 4
- AOMZRTTZRBZOAC-UHFFFAOYSA-N [1-[2-[3-phenyl-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidin-4-yl]-[1-(pyridin-2-ylmethyl)benzimidazol-2-yl]methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCN3CCC(CC3)C(=O)C=3N(C4=CC=CC=C4N=3)CC=3N=CC=CC=3)(CC2)C=2C=CC=CC=2)=C1 AOMZRTTZRBZOAC-UHFFFAOYSA-N 0.000 claims description 4
- DBTUVKKFUGAZAM-UHFFFAOYSA-N [3-(3,4-dimethoxyphenyl)-3-[2-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]ethyl]pyrrolidin-1-yl]-(3,4,5-trimethoxyphenyl)methanone Chemical compound C1=C(OC)C(OC)=CC=C1C1(CCN2CCC(CC2)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CN(C(=O)C=2C=C(OC)C(OC)=C(OC)C=2)CC1 DBTUVKKFUGAZAM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 4
- OBKMCCVDLMLCFS-UHFFFAOYSA-N 1-[3-(3,4-dichlorophenyl)-3-[2-[4-[1-(2-ethoxyethyl)benzimidazole-2-carbonyl]piperidin-1-yl]ethyl]piperidin-1-yl]-2-(3-propan-2-yloxyphenyl)ethanone Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1C(=O)C(CC1)CCN1CCC(C1)(C=2C=C(Cl)C(Cl)=CC=2)CCCN1C(=O)CC1=CC=CC(OC(C)C)=C1 OBKMCCVDLMLCFS-UHFFFAOYSA-N 0.000 claims description 3
- ZINVMVLQGZEHNI-UHFFFAOYSA-N 2-[3-[2-[1-[2-[3-phenyl-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidine-4-carbonyl]benzimidazol-1-yl]propoxy]benzoic acid Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCN3CCC(CC3)C(=O)C=3N(C4=CC=CC=C4N=3)CCCOC=3C(=CC=CC=3)C(O)=O)(CC2)C=2C=CC=CC=2)=C1 ZINVMVLQGZEHNI-UHFFFAOYSA-N 0.000 claims description 3
- KVYXGCNCFPIESF-UHFFFAOYSA-N 4-[2-[1-[2-[3-(3,4-dichlorophenyl)-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidine-4-carbonyl]benzimidazol-1-yl]butanoic acid Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCN3CCC(CC3)C(=O)C=3N(C4=CC=CC=C4N=3)CCCC(O)=O)(CC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 KVYXGCNCFPIESF-UHFFFAOYSA-N 0.000 claims description 3
- SGSDMASCYPMWHE-UHFFFAOYSA-N 4-[[2-[1-[2-[3-(3,4-dimethoxyphenyl)-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidine-4-carbonyl]benzimidazol-1-yl]methyl]benzoic acid Chemical compound C1=C(OC)C(OC)=CC=C1C1(CCN2CCC(CC2)C(=O)C=2N(C3=CC=CC=C3N=2)CC=2C=CC(=CC=2)C(O)=O)CN(C(=O)C=2C=C(OC)C(OC)=C(OC)C=2)CC1 SGSDMASCYPMWHE-UHFFFAOYSA-N 0.000 claims description 3
- ZLXCEBAWAKEHFS-UHFFFAOYSA-N 4-[[2-[1-[2-[3-phenyl-1-(3,4,5-trimethoxybenzoyl)pyrrolidin-3-yl]ethyl]piperidine-4-carbonyl]benzimidazol-1-yl]methyl]benzoic acid Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCN3CCC(CC3)C(=O)C=3N(C4=CC=CC=C4N=3)CC=3C=CC(=CC=3)C(O)=O)(CC2)C=2C=CC=CC=2)=C1 ZLXCEBAWAKEHFS-UHFFFAOYSA-N 0.000 claims description 3
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- 125000004432 carbon atom Chemical group C* 0.000 description 4
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- VWUWGEPQJXEFJR-UHFFFAOYSA-N [3-(2-hydroxyethyl)-3-(4-methoxyphenyl)pyrrolidin-1-yl]-(3,4,5-trimethoxyphenyl)methanone Chemical compound C1=CC(OC)=CC=C1C1(CCO)CN(C(=O)C=2C=C(OC)C(OC)=C(OC)C=2)CC1 VWUWGEPQJXEFJR-UHFFFAOYSA-N 0.000 description 1
- MUMLYJYRRJWFRQ-UHFFFAOYSA-N [3-(2-methylsulfonylethyl)-3-[4-(trifluoromethyl)phenyl]pyrrolidin-1-yl]-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCS(C)(=O)=O)(CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 MUMLYJYRRJWFRQ-UHFFFAOYSA-N 0.000 description 1
- XQHDASACUQCJFW-UHFFFAOYSA-N [3-(3,4-difluorophenyl)-3-(2-hydroxyethyl)pyrrolidin-1-yl]-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCO)(CC2)C=2C=C(F)C(F)=CC=2)=C1 XQHDASACUQCJFW-UHFFFAOYSA-N 0.000 description 1
- YCQORRYGFKMIRQ-UHFFFAOYSA-N [3-(3,4-dimethoxyphenyl)-3-(2-hydroxyethyl)pyrrolidin-1-yl]-phenylmethanone Chemical compound C1=C(OC)C(OC)=CC=C1C1(CCO)CN(C(=O)C=2C=CC=CC=2)CC1 YCQORRYGFKMIRQ-UHFFFAOYSA-N 0.000 description 1
- KSWWJJRYXIWDIE-UHFFFAOYSA-N [3-(3,4-dimethylphenyl)-3-(2-hydroxyethyl)pyrrolidin-1-yl]-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCO)(CC2)C=2C=C(C)C(C)=CC=2)=C1 KSWWJJRYXIWDIE-UHFFFAOYSA-N 0.000 description 1
- TXOBRLRNUKKOEA-UHFFFAOYSA-N [3-(3-chlorophenyl)-3-(2-hydroxyethyl)pyrrolidin-1-yl]-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCO)(CC2)C=2C=C(Cl)C=CC=2)=C1 TXOBRLRNUKKOEA-UHFFFAOYSA-N 0.000 description 1
- ZLTRYJQRMNFZFN-UHFFFAOYSA-N [3-(4-chlorophenyl)-3-(2-hydroxyethyl)pyrrolidin-1-yl]-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCO)(CC2)C=2C=CC(Cl)=CC=2)=C1 ZLTRYJQRMNFZFN-UHFFFAOYSA-N 0.000 description 1
- SRYLXIULSZGIBH-UHFFFAOYSA-N [3-(4-chlorophenyl)-3-(2-methylsulfonylethyl)pyrrolidin-1-yl]-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCS(C)(=O)=O)(CC2)C=2C=CC(Cl)=CC=2)=C1 SRYLXIULSZGIBH-UHFFFAOYSA-N 0.000 description 1
- VNAQVHFABYGQDC-UHFFFAOYSA-N [3-(4-fluorophenyl)-3-(2-hydroxyethyl)pyrrolidin-1-yl]-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(CCO)(CC2)C=2C=CC(F)=CC=2)=C1 VNAQVHFABYGQDC-UHFFFAOYSA-N 0.000 description 1
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- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
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- 125000000217 alkyl group Chemical group 0.000 description 1
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- CJRCJVASMQDICH-UHFFFAOYSA-N benzhydryl 4-butanoyloxy-3,5-dimethoxybenzoate Chemical compound C1=C(OC)C(OC(=O)CCC)=C(OC)C=C1C(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 CJRCJVASMQDICH-UHFFFAOYSA-N 0.000 description 1
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- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
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- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- XLMBIZDYYVRQHQ-UHFFFAOYSA-N diethyl 3-(3-chlorophenyl)-3-cyanopentanedioate Chemical compound CCOC(=O)CC(CC(=O)OCC)(C#N)C1=CC=CC(Cl)=C1 XLMBIZDYYVRQHQ-UHFFFAOYSA-N 0.000 description 1
- OSOXLOHGXMJGRZ-UHFFFAOYSA-N diethyl 3-cyano-3-pyridin-2-ylpentanedioate Chemical compound CCOC(=O)CC(CC(=O)OCC)(C#N)C1=CC=CC=N1 OSOXLOHGXMJGRZ-UHFFFAOYSA-N 0.000 description 1
- ZMISODWVFHHWNR-UHFFFAOYSA-N diphenyl(4-piperidinyl)methanol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)C1CCNCC1 ZMISODWVFHHWNR-UHFFFAOYSA-N 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- FQTIYMRSUOADDK-UHFFFAOYSA-N ethyl 3-bromopropanoate Chemical compound CCOC(=O)CCBr FQTIYMRSUOADDK-UHFFFAOYSA-N 0.000 description 1
- XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- IYWCBYFJFZCCGV-UHFFFAOYSA-N formamide;hydrate Chemical compound O.NC=O IYWCBYFJFZCCGV-UHFFFAOYSA-N 0.000 description 1
- 238000010575 fractional recrystallization Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- 150000002496 iodine Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- BSEHEAPLAGPPMR-UHFFFAOYSA-N methyl 2-(3-iodopropoxy)benzoate Chemical compound COC(=O)C1=CC=CC=C1OCCCI BSEHEAPLAGPPMR-UHFFFAOYSA-N 0.000 description 1
- POZIFRPMDFGLIW-UHFFFAOYSA-N methyl 3-cyano-2-phenylpropanoate Chemical compound COC(=O)C(CC#N)C1=CC=CC=C1 POZIFRPMDFGLIW-UHFFFAOYSA-N 0.000 description 1
- NLWBJPPMPLPZIE-UHFFFAOYSA-N methyl 4-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1 NLWBJPPMPLPZIE-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 239000001120 potassium sulphate Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003628 tricarboxylic acids Chemical class 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic 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
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- 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
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US29596094A | 1994-08-25 | 1994-08-25 | |
US50191495A | 1995-07-13 | 1995-07-13 | |
PCT/US1995/010640 WO1996006094A1 (en) | 1994-08-25 | 1995-08-17 | Novel substituted piperidines useful for the treatment of allergic diseases |
Publications (3)
Publication Number | Publication Date |
---|---|
NO970831D0 NO970831D0 (no) | 1997-02-24 |
NO970831L NO970831L (no) | 1997-04-18 |
NO313237B1 true NO313237B1 (no) | 2002-09-02 |
Family
ID=26969426
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19970831A NO313237B1 (no) | 1994-08-25 | 1997-02-24 | Nye substituerte piperidiner som er anvendbare for behandling av allergiske sykdommer og farmasöytisk preparat |
Country Status (20)
Country | Link |
---|---|
US (1) | US6329392B1 (zh) |
EP (1) | EP0777666B1 (zh) |
JP (1) | JPH10504580A (zh) |
KR (1) | KR100362620B1 (zh) |
CN (1) | CN1067385C (zh) |
AT (1) | ATE177095T1 (zh) |
AU (1) | AU693936B2 (zh) |
CA (1) | CA2198084C (zh) |
DE (1) | DE69508093T2 (zh) |
DK (1) | DK0777666T3 (zh) |
ES (1) | ES2132709T3 (zh) |
FI (1) | FI114470B (zh) |
GR (1) | GR3030253T3 (zh) |
HU (1) | HU221434B (zh) |
IL (1) | IL115040A (zh) |
MX (1) | MX9701305A (zh) |
NO (1) | NO313237B1 (zh) |
NZ (1) | NZ292683A (zh) |
TW (1) | TW430663B (zh) |
WO (1) | WO1996006094A1 (zh) |
Families Citing this family (63)
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US6211199B1 (en) | 1995-11-17 | 2001-04-03 | Aventis Pharmaceuticals Inc. | Substituted 4-(1H-benzimidazol-2-yl-amino)piperidines useful for the treatment of allergic diseases |
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US6194406B1 (en) | 1995-12-20 | 2001-02-27 | Aventis Pharmaceuticals Inc. | Substituted 4-(1H-benzimidazol-2-yl)[1,4]diazepanes useful for the treatment of allergic disease |
US6423704B2 (en) | 1995-12-20 | 2002-07-23 | Aventis Pharmaceuticals Inc. | Substituted 4-(1H-benzimidazol-2-yl)[1,4]diazepanes useful for the treatment of allergic diseases |
KR20000064487A (ko) * | 1995-12-20 | 2000-11-06 | 게리 디. 스트리트, 스티븐 엘. 네스비트 | 알레르기질환의치료에유용한신규의치환된4-(1h-벤즈이미다졸-2-일)1,4디아제판 |
US5998439A (en) | 1996-02-21 | 1999-12-07 | Hoescht Marion Roussel, Inc. | Substituted N-methyl-N-(4-(piperidin-1-yl)-2-(aryl)butyl)benzamides useful for the treatment of allergic diseases |
IL125605A0 (en) * | 1996-02-21 | 1999-03-12 | Hoechst Marion Roussel Inc | Novel substituted n-methyl-n-(4(4-(1h-benzimidazol-2-yl)[1,4]diazepan-1-yl)-2-(aryl) butyl) benzamides useful for the treatment of allergic diseases |
US5932571A (en) * | 1996-02-21 | 1999-08-03 | Hoechst Marion Roussel, Inc. | Substituted N-methyl-N-(4-(4-(1H-benzimidazol-2-yl) {1,4}diazepan-1-yl)-2-(aryl) butyl) benzamides useful for the treatment of allergic diseases |
DK0888336T3 (da) * | 1996-02-21 | 2002-12-02 | Aventis Pharma Inc | Nye substituerede N-methyl-N-(4-(4-(1H-benzimidazol-2-yl-amino)-piperidin-1-yl)-1-(aryl)butyl)benzamider til behandling af allergisygdomme |
FR2755133B1 (fr) * | 1996-10-31 | 1999-01-15 | Sanofi Sa | Nouveaux derives d'amides cycliques diversement substitues antagonistes selectifs du recepteur nk3 humain, procede pour leur obtention et compositions pharmaceutiques les contenant |
FR2759585B1 (fr) * | 1997-02-17 | 1999-06-11 | Sanofi Sa | Formulations pharmaceutiques presentees sous forme seche pour l'administration orale d'un compose ammonium quaternaire cyclique |
FR2759584B1 (fr) * | 1997-02-17 | 1999-06-11 | Sanofi Sa | Composition pharmaceutique pour l'administration orale de composes heterocycliques sous forme ammonium quaternaire |
GB9821898D0 (en) * | 1998-10-08 | 1998-12-02 | Pfizer Ltd | Heterocycles |
CN1329490A (zh) * | 1998-10-09 | 2002-01-02 | 先灵公司 | 用于治疗变应性疾病的组合物和方法 |
US6103735A (en) * | 1998-10-09 | 2000-08-15 | Schering Corporation | Composition and method for treating allergic diseases |
FR2789390B3 (fr) | 1999-02-10 | 2001-03-09 | Sanofi Sa | Nouveaux derives de piperidine, procede pour leur obtention et compositions pharmaceutiques les contenant |
BR0107624A (pt) * | 2000-01-17 | 2002-11-12 | Bayer Ag | Arilcetonas substituìdas |
JP2004532838A (ja) * | 2001-03-02 | 2004-10-28 | ブリストル−マイヤーズ スクイブ カンパニー | メラノコルチン受容体のモデュレーターとして有用な化合物及びそれを含む製薬組成物 |
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-
1995
- 1995-08-17 CN CN95195283A patent/CN1067385C/zh not_active Expired - Fee Related
- 1995-08-17 EP EP95931551A patent/EP0777666B1/en not_active Expired - Lifetime
- 1995-08-17 AT AT95931551T patent/ATE177095T1/de not_active IP Right Cessation
- 1995-08-17 JP JP8508257A patent/JPH10504580A/ja not_active Ceased
- 1995-08-17 DE DE69508093T patent/DE69508093T2/de not_active Expired - Fee Related
- 1995-08-17 NZ NZ292683A patent/NZ292683A/en unknown
- 1995-08-17 AU AU34928/95A patent/AU693936B2/en not_active Ceased
- 1995-08-17 DK DK95931551T patent/DK0777666T3/da active
- 1995-08-17 HU HU9701257A patent/HU221434B/hu not_active IP Right Cessation
- 1995-08-17 MX MX9701305A patent/MX9701305A/es unknown
- 1995-08-17 CA CA002198084A patent/CA2198084C/en not_active Expired - Fee Related
- 1995-08-17 ES ES95931551T patent/ES2132709T3/es not_active Expired - Lifetime
- 1995-08-17 WO PCT/US1995/010640 patent/WO1996006094A1/en active IP Right Grant
- 1995-08-17 KR KR1019970701189A patent/KR100362620B1/ko not_active IP Right Cessation
- 1995-08-23 IL IL11504095A patent/IL115040A/xx not_active IP Right Cessation
- 1995-08-23 TW TW084108797A patent/TW430663B/zh not_active IP Right Cessation
-
1997
- 1997-02-24 FI FI970771A patent/FI114470B/fi not_active IP Right Cessation
- 1997-02-24 NO NO19970831A patent/NO313237B1/no unknown
-
1998
- 1998-05-15 US US09/079,924 patent/US6329392B1/en not_active Expired - Fee Related
-
1999
- 1999-05-19 GR GR990401346T patent/GR3030253T3/el unknown
Also Published As
Publication number | Publication date |
---|---|
FI114470B (fi) | 2004-10-29 |
CA2198084C (en) | 2000-03-28 |
IL115040A0 (en) | 1995-12-08 |
DK0777666T3 (da) | 1999-09-27 |
NO970831L (no) | 1997-04-18 |
FI970771A (fi) | 1997-02-24 |
WO1996006094A1 (en) | 1996-02-29 |
HUT76644A (en) | 1997-10-28 |
TW430663B (en) | 2001-04-21 |
KR100362620B1 (ko) | 2003-02-14 |
HU221434B (en) | 2002-10-28 |
ATE177095T1 (de) | 1999-03-15 |
JPH10504580A (ja) | 1998-05-06 |
AU3492895A (en) | 1996-03-14 |
GR3030253T3 (en) | 1999-08-31 |
NZ292683A (en) | 1998-07-28 |
CN1067385C (zh) | 2001-06-20 |
DE69508093T2 (de) | 1999-07-15 |
EP0777666B1 (en) | 1999-03-03 |
IL115040A (en) | 2000-02-29 |
ES2132709T3 (es) | 1999-08-16 |
AU693936B2 (en) | 1998-07-09 |
US6329392B1 (en) | 2001-12-11 |
CA2198084A1 (en) | 1996-02-29 |
FI970771A0 (fi) | 1997-02-24 |
KR970705556A (ko) | 1997-10-09 |
NO970831D0 (no) | 1997-02-24 |
DE69508093D1 (de) | 1999-04-08 |
MX9701305A (es) | 1998-05-31 |
EP0777666A1 (en) | 1997-06-11 |
CN1158612A (zh) | 1997-09-03 |
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