RU2009120229A - Производные хинуклидинола в качестве антагонистов мускариновых рецепторов - Google Patents
Производные хинуклидинола в качестве антагонистов мускариновых рецепторов Download PDFInfo
- Publication number
- RU2009120229A RU2009120229A RU2009120229/15A RU2009120229A RU2009120229A RU 2009120229 A RU2009120229 A RU 2009120229A RU 2009120229/15 A RU2009120229/15 A RU 2009120229/15A RU 2009120229 A RU2009120229 A RU 2009120229A RU 2009120229 A RU2009120229 A RU 2009120229A
- Authority
- RU
- Russia
- Prior art keywords
- oxy
- azoniabicyclo
- octane
- alkyl
- phenyl
- Prior art date
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- FSNYTEYOTCTPSO-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-2-ol Chemical class C1CN2C(O)CC1CC2 FSNYTEYOTCTPSO-UHFFFAOYSA-N 0.000 title 1
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 title 1
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 title 1
- 239000005557 antagonist Substances 0.000 title 1
- 125000001424 substituent group Chemical group 0.000 claims abstract 39
- 229910052736 halogen Inorganic materials 0.000 claims abstract 36
- 150000002367 halogens Chemical class 0.000 claims abstract 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 33
- 150000001875 compounds Chemical class 0.000 claims abstract 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract 19
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 10
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract 9
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract 9
- 125000001931 aliphatic group Chemical group 0.000 claims abstract 7
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract 3
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 claims abstract 3
- 125000005842 heteroatom Chemical group 0.000 claims abstract 3
- 239000001301 oxygen Substances 0.000 claims abstract 3
- 229910052717 sulfur Inorganic materials 0.000 claims abstract 3
- 239000011593 sulfur Chemical group 0.000 claims abstract 3
- 125000002947 alkylene group Chemical group 0.000 claims abstract 2
- 229910052799 carbon Inorganic materials 0.000 claims abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims 61
- 125000003545 alkoxy group Chemical group 0.000 claims 15
- -1 R 21 Chemical compound 0.000 claims 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 5
- 239000002253 acid Substances 0.000 claims 5
- 229910052739 hydrogen Inorganic materials 0.000 claims 5
- 239000001257 hydrogen Substances 0.000 claims 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 4
- 125000001072 heteroaryl group Chemical group 0.000 claims 4
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 3
- 150000001450 anions Chemical class 0.000 claims 3
- 238000000034 method Methods 0.000 claims 3
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 2
- 239000002671 adjuvant Substances 0.000 claims 2
- 125000004122 cyclic group Chemical group 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 125000001544 thienyl group Chemical group 0.000 claims 2
- UGRMITBWUVWUEB-UHFFFAOYSA-N 1-$l^{1}-oxidanyl-3-methylbenzene Chemical group CC1=CC=CC([O])=C1 UGRMITBWUVWUEB-UHFFFAOYSA-N 0.000 claims 1
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims 1
- 125000003163 2-(2-naphthyl)ethyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(C([H])=C([H])C2=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000006516 2-(benzyloxy)ethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 1
- 125000000979 2-amino-2-oxoethyl group Chemical group [H]C([*])([H])C(=O)N([H])[H] 0.000 claims 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims 1
- JFUAWXPBHXKZGA-IBGZPJMESA-N 4-fluoro-2-[(4r)-5,5,5-trifluoro-4-hydroxy-2-methyl-4-(1h-pyrrolo[2,3-c]pyridin-2-ylmethyl)pentan-2-yl]phenol Chemical compound C([C@@](O)(CC=1NC2=CN=CC=C2C=1)C(F)(F)F)C(C)(C)C1=CC(F)=CC=C1O JFUAWXPBHXKZGA-IBGZPJMESA-N 0.000 claims 1
- 102100039705 Beta-2 adrenergic receptor Human genes 0.000 claims 1
- 102000009410 Chemokine receptor Human genes 0.000 claims 1
- 108050000299 Chemokine receptor Proteins 0.000 claims 1
- 102000003676 Glucocorticoid Receptors Human genes 0.000 claims 1
- 108090000079 Glucocorticoid Receptors Proteins 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 241001465754 Metazoa Species 0.000 claims 1
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 claims 1
- 108091000080 Phosphotransferase Proteins 0.000 claims 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims 1
- QTALOFSYVIUAQG-VCNRBZFXSA-N [(3r)-1-(1,3-benzothiazol-2-ylmethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC=2SC3=CC=CC=C3N=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 QTALOFSYVIUAQG-VCNRBZFXSA-N 0.000 claims 1
- WKMMKXONQAAZDT-WKCBJSDVSA-O [(3r)-1-(2-amino-2-oxoethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC(N)=O)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 WKMMKXONQAAZDT-WKCBJSDVSA-O 0.000 claims 1
- NEPJGZHPAZSMNQ-IKMXCIGBSA-O [(3r)-1-(2-anilino-2-oxoethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-(azepan-1-yl)-2-phenylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC(=O)NC=2C=CC=CC=2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCCCCC1 NEPJGZHPAZSMNQ-IKMXCIGBSA-O 0.000 claims 1
- VAEJXCRKXKTGOE-GBEVRHLJSA-O [(3r)-1-(2-anilino-2-oxoethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC(=O)NC=2C=CC=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 VAEJXCRKXKTGOE-GBEVRHLJSA-O 0.000 claims 1
- RKSCZVHQYFYRQE-QUDWSAQTSA-N [(3r)-1-(2-cyclohexylethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCC2CCCCC2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 RKSCZVHQYFYRQE-QUDWSAQTSA-N 0.000 claims 1
- JLZUQVIDTJVTHP-LOXOKPPFSA-N [(3r)-1-(2-phenylethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-(azepan-1-yl)-2-phenylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCC=2C=CC=CC=2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCCCCC1 JLZUQVIDTJVTHP-LOXOKPPFSA-N 0.000 claims 1
- GVBIYOSUGYZYCM-NJHLQHIQSA-N [(3r)-1-(2-phenylethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-phenyl-2-thiomorpholin-4-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCC=2C=CC=CC=2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCSCC1 GVBIYOSUGYZYCM-NJHLQHIQSA-N 0.000 claims 1
- BBIBFZJMAOWDKQ-QUDWSAQTSA-N [(3r)-1-(2-phenylethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCC=2C=CC=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 BBIBFZJMAOWDKQ-QUDWSAQTSA-N 0.000 claims 1
- OUWAAHAJKBQWQO-CBGFLSBTSA-N [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-(4-chlorophenyl)-2-(3,3-dimethylazetidin-1-yl)propanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCOC=2C=CC=CC=2)C1)C(=O)C(C=1C=CC(Cl)=CC=1)(C)N1CC(C)(C)C1 OUWAAHAJKBQWQO-CBGFLSBTSA-N 0.000 claims 1
- VYNALOWTXOAZBL-ZKFMWTABSA-N [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-(azepan-1-yl)-2-phenylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCOC=2C=CC=CC=2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCCCCC1 VYNALOWTXOAZBL-ZKFMWTABSA-N 0.000 claims 1
- RVXKMYHNDBHDLD-XGWPGLATSA-N [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-phenyl-2-piperidin-1-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCOC=2C=CC=CC=2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCCCC1 RVXKMYHNDBHDLD-XGWPGLATSA-N 0.000 claims 1
- STHQIPGVDFWSPS-RKIJJWRQSA-N [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-phenyl-2-thiomorpholin-4-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCOC=2C=CC=CC=2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCSCC1 STHQIPGVDFWSPS-RKIJJWRQSA-N 0.000 claims 1
- BPQXYDWWAMKJMI-YBTWUVFZSA-N [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-thiomorpholin-4-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCOC=2C=CC=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCSCC1 BPQXYDWWAMKJMI-YBTWUVFZSA-N 0.000 claims 1
- KPJUFSMOBZZJTC-WHVMCNGOSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-(azepan-1-yl)-2-phenylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCC=2C=CC=CC=2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCCCCC1 KPJUFSMOBZZJTC-WHVMCNGOSA-N 0.000 claims 1
- CKERXQXYNOQRIE-JPPQEZTKSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-phenyl-2-thiomorpholin-4-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCC=2C=CC=CC=2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCSCC1 CKERXQXYNOQRIE-JPPQEZTKSA-N 0.000 claims 1
- ZDMIIYGPOIOKNJ-OXSYTJCYSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCC=2C=CC=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 ZDMIIYGPOIOKNJ-OXSYTJCYSA-N 0.000 claims 1
- OFJGZJVLDFQCRT-QUDWSAQTSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-thiomorpholin-4-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCC=2C=CC=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCSCC1 OFJGZJVLDFQCRT-QUDWSAQTSA-N 0.000 claims 1
- NKFSGQZUJGOLHM-ZYMCSTCLSA-N [(3r)-1-(3-pyridin-3-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-(azepan-1-yl)-2-phenylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCC=2C=NC=CC=2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCCCCC1 NKFSGQZUJGOLHM-ZYMCSTCLSA-N 0.000 claims 1
- LDMUCNIFYVJOTG-FCOBLWCLSA-N [(3r)-1-(3-pyridin-4-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCC=2C=CN=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 LDMUCNIFYVJOTG-FCOBLWCLSA-N 0.000 claims 1
- JKZTXAFKMWAXLC-QKZQWPARSA-N [(3r)-1-(4-phenylbutyl)-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-phenyl-2-piperidin-1-ylpropanoate Chemical compound N1([C@](C)(C(=O)O[C@@H]2C3CC[N+](CC3)(CCCCC=3C=CC=CC=3)C2)C=2C=CC=CC=2)CCCCC1 JKZTXAFKMWAXLC-QKZQWPARSA-N 0.000 claims 1
- ABIVXWKXMJCZMZ-MYUDZCHNSA-N [(3r)-1-(4-phenylbutyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCCC=2C=CC=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 ABIVXWKXMJCZMZ-MYUDZCHNSA-N 0.000 claims 1
- CDCDYSQNFFEOBO-CPGZBMCBSA-N [(3r)-1-[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC=2ON=C(N=2)C=2C=CC=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 CDCDYSQNFFEOBO-CPGZBMCBSA-N 0.000 claims 1
- IRAOTBKCIFRJHZ-WRZLWCPGSA-N [(3r)-1-[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-thiomorpholin-4-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC=2ON=C(N=2)C=2C=CC=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCSCC1 IRAOTBKCIFRJHZ-WRZLWCPGSA-N 0.000 claims 1
- YQRDRLDGLPKZQU-HVZIFNFOSA-N [(3r)-1-[(3r)-3-hydroxy-3-phenylpropyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-phenyl-2-piperidin-1-ylpropanoate Chemical compound N1([C@](C)(C(=O)O[C@@H]2C3CC[N+](CC3)(CC[C@@H](O)C=3C=CC=CC=3)C2)C=2C=CC=CC=2)CCCCC1 YQRDRLDGLPKZQU-HVZIFNFOSA-N 0.000 claims 1
- DOBNHUAQAMSKSA-PYIACWHASA-O [(3r)-1-[2-(1,2-benzoxazol-3-ylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC(=O)NC=2C3=CC=CC=C3ON=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 DOBNHUAQAMSKSA-PYIACWHASA-O 0.000 claims 1
- FWGZCGKLVODFPY-ZKZAZUJQSA-O [(3r)-1-[2-(1,2-oxazol-3-ylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-phenyl-2-piperidin-1-ylpropanoate Chemical compound N1([C@](C)(C(=O)O[C@@H]2C3CC[N+](CC3)(CC(=O)NC3=NOC=C3)C2)C=2C=CC=CC=2)CCCCC1 FWGZCGKLVODFPY-ZKZAZUJQSA-O 0.000 claims 1
- MMJKYOJSJOKWLE-GLDZRGHBSA-O [(3r)-1-[2-(1,2-oxazol-3-ylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-(azepan-1-yl)-2-phenylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC(=O)NC2=NOC=C2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCCCCC1 MMJKYOJSJOKWLE-GLDZRGHBSA-O 0.000 claims 1
- CFNPNMRTNOMPND-SQJIEPIVSA-O [(3r)-1-[2-(1,2-oxazol-3-ylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-phenyl-2-thiomorpholin-4-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC(=O)NC2=NOC=C2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCSCC1 CFNPNMRTNOMPND-SQJIEPIVSA-O 0.000 claims 1
- STBUKKKWQRDACN-SBYBOYLISA-O [(3r)-1-[2-(1,2-oxazol-3-ylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC(=O)NC2=NOC=C2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 STBUKKKWQRDACN-SBYBOYLISA-O 0.000 claims 1
- HLRWWFFFSFTUPE-JLGGAKIXSA-N [(3r)-1-[2-(3-chlorophenyl)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-phenyl-2-piperidin-1-ylpropanoate Chemical compound N1([C@](C)(C(=O)O[C@@H]2C3CC[N+](CC3)(CC(=O)C=3C=C(Cl)C=CC=3)C2)C=2C=CC=CC=2)CCCCC1 HLRWWFFFSFTUPE-JLGGAKIXSA-N 0.000 claims 1
- DYNJLEKGXRTDOQ-NNMXADRKSA-N [(3r)-1-[2-(3-chlorophenyl)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-phenyl-2-piperidin-1-ylpropanoate Chemical compound N1([C@](C)(C(=O)O[C@@H]2C3CC[N+](CC3)(CCC=3C=C(Cl)C=CC=3)C2)C=2C=CC=CC=2)CCCCC1 DYNJLEKGXRTDOQ-NNMXADRKSA-N 0.000 claims 1
- WMWWHRPKFUUOCF-IBGIQVRPSA-N [(3r)-1-[2-(3-chlorophenyl)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-(azepan-1-yl)-2-phenylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCC=2C=C(Cl)C=CC=2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCCCCC1 WMWWHRPKFUUOCF-IBGIQVRPSA-N 0.000 claims 1
- ODPLOFLCPZJAHL-AEIVBJPJSA-N [(3r)-1-[2-(3-chlorophenyl)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-morpholin-4-yl-2-phenylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCC=2C=C(Cl)C=CC=2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCOCC1 ODPLOFLCPZJAHL-AEIVBJPJSA-N 0.000 claims 1
- UYPLAXJUEPUGFP-AEIVBJPJSA-N [(3r)-1-[2-(3-chlorophenyl)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-phenyl-2-thiomorpholin-4-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCC=2C=C(Cl)C=CC=2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCSCC1 UYPLAXJUEPUGFP-AEIVBJPJSA-N 0.000 claims 1
- HUYMQVAQICPEIT-OSRBFEJNSA-N [(3r)-1-[2-(3-chlorophenyl)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCC=2C=C(Cl)C=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 HUYMQVAQICPEIT-OSRBFEJNSA-N 0.000 claims 1
- WLYMTYXQESBJKG-VHTXSSKDSA-N [(3r)-1-[2-(3-chlorophenyl)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-thiomorpholin-4-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCC=2C=C(Cl)C=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCSCC1 WLYMTYXQESBJKG-VHTXSSKDSA-N 0.000 claims 1
- ITTMDEAJVJKWJA-FVWPEXKFSA-O [(3r)-1-[2-(3-fluoroanilino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-(azepan-1-yl)-2-phenylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC(=O)NC=2C=C(F)C=CC=2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCCCCC1 ITTMDEAJVJKWJA-FVWPEXKFSA-O 0.000 claims 1
- VZNXMVGDWIFGPG-CLPKMKQYSA-O [(3r)-1-[2-(3-fluoroanilino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC(=O)NC=2C=C(F)C=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 VZNXMVGDWIFGPG-CLPKMKQYSA-O 0.000 claims 1
- YBXSBMAXTJMFMN-SSPRTNKYSA-O [(3r)-1-[2-(3-fluoroanilino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-thiomorpholin-4-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC(=O)NC=2C=C(F)C=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCSCC1 YBXSBMAXTJMFMN-SSPRTNKYSA-O 0.000 claims 1
- HMTTYBJNFKZGLV-JLGGAKIXSA-N [(3r)-1-[2-(3-fluorophenyl)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-phenyl-2-piperidin-1-ylpropanoate Chemical compound N1([C@](C)(C(=O)O[C@@H]2C3CC[N+](CC3)(CC(=O)C=3C=C(F)C=CC=3)C2)C=2C=CC=CC=2)CCCCC1 HMTTYBJNFKZGLV-JLGGAKIXSA-N 0.000 claims 1
- YZQCWYODZZPOCX-IBGIQVRPSA-N [(3r)-1-[2-(3-fluorophenyl)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-(azepan-1-yl)-2-phenylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCC=2C=C(F)C=CC=2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCCCCC1 YZQCWYODZZPOCX-IBGIQVRPSA-N 0.000 claims 1
- MZAVVLWULQNHMR-OSRBFEJNSA-N [(3r)-1-[2-(3-fluorophenyl)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCC=2C=C(F)C=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 MZAVVLWULQNHMR-OSRBFEJNSA-N 0.000 claims 1
- AOSUZFQOXUBKAY-VHTXSSKDSA-N [(3r)-1-[2-(3-fluorophenyl)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-thiomorpholin-4-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCC=2C=C(F)C=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCSCC1 AOSUZFQOXUBKAY-VHTXSSKDSA-N 0.000 claims 1
- QKGOMZQSQGYDAX-MCZUWTTOSA-N [(3r)-1-[2-(3-methoxyphenyl)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-phenyl-2-piperidin-1-ylpropanoate Chemical compound COC1=CC=CC(C(=O)C[N+]23CCC(CC2)[C@H](C3)OC(=O)[C@@](C)(N2CCCCC2)C=2C=CC=CC=2)=C1 QKGOMZQSQGYDAX-MCZUWTTOSA-N 0.000 claims 1
- FNYFFCOCVNTJCD-NNMXADRKSA-N [(3r)-1-[2-(4-fluorophenyl)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-phenyl-2-piperidin-1-ylpropanoate Chemical compound N1([C@](C)(C(=O)O[C@@H]2C3CC[N+](CC3)(CCC=3C=CC(F)=CC=3)C2)C=2C=CC=CC=2)CCCCC1 FNYFFCOCVNTJCD-NNMXADRKSA-N 0.000 claims 1
- JJLFLKPJIGRQQY-SHZVQYQYSA-N [(3r)-1-[2-(4-methylphenyl)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-phenyl-2-piperidin-1-ylpropanoate Chemical compound C1=CC(C)=CC=C1C(=O)C[N+]1(C[C@@H]2OC(=O)[C@@](C)(N3CCCCC3)C=3C=CC=CC=3)CCC2CC1 JJLFLKPJIGRQQY-SHZVQYQYSA-N 0.000 claims 1
- MGBXGVBXVMTGHH-FUNPEOAZSA-O [(3r)-1-[2-[(5-methylpyrazin-2-yl)amino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-(azepan-1-yl)-2-phenylpropanoate Chemical compound C1=NC(C)=CN=C1NC(=O)C[N+]1(C[C@@H]2OC(=O)C(C)(N3CCCCCC3)C=3C=CC=CC=3)CCC2CC1 MGBXGVBXVMTGHH-FUNPEOAZSA-O 0.000 claims 1
- LBLCBTYBHPREDB-MRJGMRHYSA-O [(3r)-1-[2-[(5-methylpyrazin-2-yl)amino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound C1=NC(C)=CN=C1NC(=O)C[N+]1(C[C@@H]2OC(=O)C(C)(N3CCCCC3)C=3SC=CC=3)CCC2CC1 LBLCBTYBHPREDB-MRJGMRHYSA-O 0.000 claims 1
- FNLYMMFDVOHLPL-PKLFASRISA-O [(3r)-1-[2-[(6-chloropyrazin-2-yl)amino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC(=O)NC=2N=C(Cl)C=NC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 FNLYMMFDVOHLPL-PKLFASRISA-O 0.000 claims 1
- YEHYTHHNLWZLCM-PKLFASRISA-O [(3r)-1-[2-[(6-chloropyridazin-3-yl)amino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC(=O)NC=2N=NC(Cl)=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 YEHYTHHNLWZLCM-PKLFASRISA-O 0.000 claims 1
- FIBKUUSMHXMGDA-NCIMKBTISA-O [(3r)-1-[2-oxo-2-([1,2,4]triazolo[1,5-a]pyridin-6-ylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-phenyl-2-piperidin-1-ylpropanoate Chemical compound N1([C@](C)(C(=O)O[C@@H]2C3CC[N+](CC3)(CC(=O)NC3=CN4N=CN=C4C=C3)C2)C=2C=CC=CC=2)CCCCC1 FIBKUUSMHXMGDA-NCIMKBTISA-O 0.000 claims 1
- HBESSADZMVANJT-JDSZFFLXSA-O [(3r)-1-[2-oxo-2-(pyrazin-2-ylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-phenyl-2-piperidin-1-ylpropanoate Chemical compound N1([C@](C)(C(=O)O[C@@H]2C3CC[N+](CC3)(CC(=O)NC=3N=CC=NC=3)C2)C=2C=CC=CC=2)CCCCC1 HBESSADZMVANJT-JDSZFFLXSA-O 0.000 claims 1
- YLKBDKNPQFQRHQ-MJOZUZDFSA-O [(3r)-1-[2-oxo-2-(pyrazin-2-ylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-thiomorpholin-4-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC(=O)NC=2N=CC=NC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCSCC1 YLKBDKNPQFQRHQ-MJOZUZDFSA-O 0.000 claims 1
- RIMUVXFPXPFFCV-JDSZFFLXSA-O [(3r)-1-[2-oxo-2-(pyridazin-3-ylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-phenyl-2-piperidin-1-ylpropanoate Chemical compound N1([C@](C)(C(=O)O[C@@H]2C3CC[N+](CC3)(CC(=O)NC=3N=NC=CC=3)C2)C=2C=CC=CC=2)CCCCC1 RIMUVXFPXPFFCV-JDSZFFLXSA-O 0.000 claims 1
- UVFCCUHZMNYBPT-QXTMRLIBSA-O [(3r)-1-[2-oxo-2-(pyridazin-3-ylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-phenyl-2-thiomorpholin-4-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CC(=O)NC=2N=NC=CC=2)C1)C(=O)C(C=1C=CC=CC=1)(C)N1CCSCC1 UVFCCUHZMNYBPT-QXTMRLIBSA-O 0.000 claims 1
- SBXBQRYZOXPPSA-LNMNIKDISA-N [(3r)-1-[3-(4-fluorophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCOC=2C=CC(F)=CC=2)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 SBXBQRYZOXPPSA-LNMNIKDISA-N 0.000 claims 1
- RCMLLLUFLCQDFY-CUTNPLARSA-N [(3r)-1-[3-[5-(trifluoromethyl)pyridin-2-yl]oxypropyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-piperidin-1-yl-2-thiophen-2-ylpropanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCOC=2N=CC(=CC=2)C(F)(F)F)C1)C(=O)C(C=1SC=CC=1)(C)N1CCCCC1 RCMLLLUFLCQDFY-CUTNPLARSA-N 0.000 claims 1
- 150000008065 acid anhydrides Chemical class 0.000 claims 1
- 239000000048 adrenergic agonist Substances 0.000 claims 1
- 229940126157 adrenergic receptor agonist Drugs 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- 125000005907 alkyl ester group Chemical group 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 125000003725 azepanyl group Chemical group 0.000 claims 1
- 125000002393 azetidinyl group Chemical group 0.000 claims 1
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 229940124750 glucocorticoid receptor agonist Drugs 0.000 claims 1
- 150000004820 halides Chemical class 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 230000003993 interaction Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000002757 morpholinyl group Chemical group 0.000 claims 1
- 125000001624 naphthyl group Chemical group 0.000 claims 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 229940127557 pharmaceutical product Drugs 0.000 claims 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 claims 1
- 102000020233 phosphotransferase Human genes 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 230000003637 steroidlike Effects 0.000 claims 1
- 150000003431 steroids Chemical class 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 3
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 abstract 2
- 0 CC(*)(C(OC)=O)N(C)* Chemical compound CC(*)(C(OC)=O)N(C)* 0.000 description 1
Classifications
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- C07—ORGANIC CHEMISTRY
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- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
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Cited By (1)
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| RU2628082C2 (ru) * | 2011-12-30 | 2017-08-14 | КЬЕЗИ ФАРМАЧЕУТИЧИ С.п.А. | Хинуклидиновые эфиры 1-азагетероциклилуксусной кислоты в качестве антимускариновых средств, способ их получения и их лекарственные композиции |
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| GB0808707D0 (en) * | 2008-05-13 | 2008-06-18 | Argenta Discovery Ltd | New compounds 275 |
| JP4837800B2 (ja) | 2008-05-13 | 2011-12-14 | アストラゼネカ・アクチエボラーグ | ムスカリンm3受容体アンタゴニストとしてのキヌクリジン誘導体 |
| WO2009153536A1 (en) * | 2008-06-17 | 2009-12-23 | Argenta Discovery Limited | 1-aza-bicyclo [2.2.2] octane derivatives useful as muscarinic receptor antagonists |
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| EP2459524A2 (en) | 2009-07-31 | 2012-06-06 | Cadila Healthcare Limited | Novel compounds as modulators of glucocorticoid receptors |
| WO2011073662A1 (en) | 2009-12-17 | 2011-06-23 | Astrazeneca Ab | Combination of a benzoxazinone and a further agent for treating respiratory diseases |
| CA2803433A1 (en) * | 2010-06-22 | 2011-12-29 | Chiesi Farmaceutici S.P.A. | Alkaloid aminoester derivatives and medicinal composition thereof |
| ES2545812T3 (es) * | 2010-06-22 | 2015-09-16 | Chiesi Farmaceutici S.P.A. | Derivados aminoéster de alcaloides y composición medicinal de estos |
| EP3023424B1 (en) * | 2013-07-13 | 2019-02-27 | Beijing Shuobai Pharmaceutical Co., Ltd. | Quinine compounds, and optical isomers, preparation method and medical use thereof |
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| GB8334494D0 (en) | 1983-12-24 | 1984-02-01 | Tanabe Seiyaku Co | Carbostyril derivatives |
| GB8923590D0 (en) * | 1989-10-19 | 1989-12-06 | Pfizer Ltd | Antimuscarinic bronchodilators |
| GR1001529B (el) | 1990-09-07 | 1994-03-31 | Elmuquimica Farm Sl | Μέ?οδος για την λήψη νέων 21-εστέρων της 16-17-ακετάλης της πρ να-1,4-διενο-3,20-διόνης. |
| GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| WO1997030035A1 (en) | 1996-02-13 | 1997-08-21 | Zeneca Limited | Quinazoline derivatives as vegf inhibitors |
| PT885198E (pt) | 1996-03-05 | 2002-06-28 | Astrazeneca Ab | Derivados de 4-anilinoquinazolina |
| GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2628082C2 (ru) * | 2011-12-30 | 2017-08-14 | КЬЕЗИ ФАРМАЧЕУТИЧИ С.п.А. | Хинуклидиновые эфиры 1-азагетероциклилуксусной кислоты в качестве антимускариновых средств, способ их получения и их лекарственные композиции |
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| CN101610813A (zh) | 2009-12-23 |
| EP2121137B1 (en) | 2012-04-25 |
| MX2009006018A (es) | 2009-06-16 |
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