JP2007529444A5 - - Google Patents
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- Publication number
- JP2007529444A5 JP2007529444A5 JP2007503242A JP2007503242A JP2007529444A5 JP 2007529444 A5 JP2007529444 A5 JP 2007529444A5 JP 2007503242 A JP2007503242 A JP 2007503242A JP 2007503242 A JP2007503242 A JP 2007503242A JP 2007529444 A5 JP2007529444 A5 JP 2007529444A5
- Authority
- JP
- Japan
- Prior art keywords
- hydroxy
- azoniabicyclo
- ylacetoxy
- dithien
- octane bromide
- 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.)
- Withdrawn
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- -1 —O (CO) R 1 Chemical group 0.000 claims description 47
- 150000001875 compounds Chemical class 0.000 claims description 33
- 125000002619 bicyclic group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- OFIWZJORXIJIHD-AEDYTTQKSA-M [(3r)-1-(4-methylpent-3-enyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 6,11-dihydro-5h-dibenzo[1,2-a:1',2'-e][7]annulene-11-carboxylate;bromide Chemical compound [Br-].C12=CC=CC=C2CCC2=CC=CC=C2C1C(=O)O[C@@H](C1)C2CC[N+]1(CCC=C(C)C)CC2 OFIWZJORXIJIHD-AEDYTTQKSA-M 0.000 claims 5
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 208000023504 respiratory system disease Diseases 0.000 claims 4
- 208000018522 Gastrointestinal disease Diseases 0.000 claims 3
- 208000012931 Urologic disease Diseases 0.000 claims 3
- 125000003342 alkenyl group Chemical group 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
- 208000035475 disorder Diseases 0.000 claims 3
- 229910052757 nitrogen Inorganic materials 0.000 claims 3
- 230000000241 respiratory effect Effects 0.000 claims 3
- 208000014001 urinary system disease Diseases 0.000 claims 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 2
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims 2
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
- 241001465754 Metazoa Species 0.000 claims 2
- 150000001721 carbon Chemical group 0.000 claims 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 2
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 claims 2
- 238000006467 substitution reaction Methods 0.000 claims 2
- FCDWBPJICFBAHM-WTHDWRSPSA-M 2,2,2-trifluoroacetate;[(3r)-1-(4,4,4-trifluorobutyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(CCCC(F)(F)F)C1)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 FCDWBPJICFBAHM-WTHDWRSPSA-M 0.000 claims 1
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims 1
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims 1
- QEZNFCFRXVYRPJ-PKMIAXOUSA-M [(3r)-1-(2-ethoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;bromide Chemical compound [Br-].O([C@@H]1C2CC[N+](CC2)(C1)CCOCC)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 QEZNFCFRXVYRPJ-PKMIAXOUSA-M 0.000 claims 1
- OCIQVDMXKYYTKI-XBQFSNPJSA-M [(3r)-1-(2-hydroxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 9-hydroxyfluorene-9-carboxylate;bromide Chemical compound [Br-].C12=CC=CC=C2C2=CC=CC=C2C1(O)C(=O)O[C@@H](C1)C2CC[N+]1(CCO)CC2 OCIQVDMXKYYTKI-XBQFSNPJSA-M 0.000 claims 1
- JYDVVIWQLIIBQB-RQUQABEPSA-M [(3r)-1-(2-hydroxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 9-methylfluorene-9-carboxylate;bromide Chemical compound [Br-].C12=CC=CC=C2C2=CC=CC=C2C1(C)C(=O)O[C@@H]1C(CC2)CC[N+]2(CCO)C1 JYDVVIWQLIIBQB-RQUQABEPSA-M 0.000 claims 1
- DOAOQUYASQYVFY-BAXVMJNZSA-M [(3r)-1-(3-cyanopropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(CCCC#N)C1)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 DOAOQUYASQYVFY-BAXVMJNZSA-M 0.000 claims 1
- FRVHIWJMJYUSLJ-LWCCLMHTSA-M [(3r)-1-(3-cyclohexylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCCC1CCCCC1 FRVHIWJMJYUSLJ-LWCCLMHTSA-M 0.000 claims 1
- OODBSQHURXBGOF-YVCYZZIKSA-M [(3r)-1-(3-hydroxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-cyclopentyl-2-hydroxy-2-thiophen-2-ylacetate;bromide Chemical compound [Br-].C1([C@](O)(C(=O)O[C@@H]2C3CC[N+](CC3)(C2)CCCO)C=2SC=CC=2)CCCC1 OODBSQHURXBGOF-YVCYZZIKSA-M 0.000 claims 1
- RNLHFMUTLYCCQG-DMEOCDBTSA-M [(3r)-1-(3-hydroxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CCCO)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 RNLHFMUTLYCCQG-DMEOCDBTSA-M 0.000 claims 1
- AQMZNDWFKMPXOH-ZMDRYIOLSA-M [(3r)-1-(4-acetyloxybutyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CCCCOC(=O)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 AQMZNDWFKMPXOH-ZMDRYIOLSA-M 0.000 claims 1
- CHVXZTXHAAJWIS-SPVPNRHKSA-M [(3r)-1-(4-cyanobutyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(CCCCC#N)C1)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 CHVXZTXHAAJWIS-SPVPNRHKSA-M 0.000 claims 1
- FNBAGXKOHRXSBP-LTBDERDOSA-M [(3r)-1-(4-hydroxybutyl)-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-cyclopentyl-2-hydroxy-2-thiophen-2-ylacetate;bromide Chemical compound [Br-].C1([C@](O)(C(=O)O[C@@H]2C3CC[N+](CC3)(C2)CCCCO)C=2SC=CC=2)CCCC1 FNBAGXKOHRXSBP-LTBDERDOSA-M 0.000 claims 1
- RHINLLSIDQNKML-PKMIAXOUSA-M [(3r)-1-(4-hydroxybutyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CCCCO)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 RHINLLSIDQNKML-PKMIAXOUSA-M 0.000 claims 1
- UXLAAHQCYFMMMT-YZQVOACISA-M [(3r)-1-(5-hydroxypentyl)-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-cyclopentyl-2-hydroxy-2-thiophen-2-ylacetate;bromide Chemical compound [Br-].C1([C@](O)(C(=O)O[C@@H]2C3CC[N+](CC3)(C2)CCCCCO)C=2SC=CC=2)CCCC1 UXLAAHQCYFMMMT-YZQVOACISA-M 0.000 claims 1
- YDXATORSQGXNSO-CBTJMOJFSA-M [(3r)-1-(6-cyanohexyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(CCCCCCC#N)C1)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 YDXATORSQGXNSO-CBTJMOJFSA-M 0.000 claims 1
- IWDCKMRRNRQUIG-NHMHNLMRSA-M [(3r)-1-(6-hydroxyhexyl)-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-cyclopentyl-2-hydroxy-2-thiophen-2-ylacetate;bromide Chemical compound [Br-].C1([C@](O)(C(=O)O[C@@H]2C3CC[N+](CC3)(C2)CCCCCCO)C=2SC=CC=2)CCCC1 IWDCKMRRNRQUIG-NHMHNLMRSA-M 0.000 claims 1
- OVRZYNONPJYUMB-VQRHYKMASA-M [(3r)-1-(cyclohexylmethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CC1CCCCC1 OVRZYNONPJYUMB-VQRHYKMASA-M 0.000 claims 1
- AFCIJPDTTQIMAA-PKMIAXOUSA-M [(3r)-1-(cyclopropylmethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CC1CC1 AFCIJPDTTQIMAA-PKMIAXOUSA-M 0.000 claims 1
- KETUMZMKPKEWJF-ICPJBOQOSA-M [(3r)-1-(oxiran-2-ylmethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CC1CO1 KETUMZMKPKEWJF-ICPJBOQOSA-M 0.000 claims 1
- QRMSJPGXGOHTGP-BAXVMJNZSA-M [(3r)-1-[2-(1,3-dioxolan-2-yl)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCC1OCCO1 QRMSJPGXGOHTGP-BAXVMJNZSA-M 0.000 claims 1
- SWGFHMHYAVOOMG-JZFOKUBASA-M [(3r)-1-[2-(1,3-dioxolan-2-yl)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 9-hydroxyfluorene-9-carboxylate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)C3(O)C4=CC=CC=C4C4=CC=CC=C43)[N+]21CCC1OCCO1 SWGFHMHYAVOOMG-JZFOKUBASA-M 0.000 claims 1
- JKLZVZUDRASWQQ-LTBDERDOSA-M [(3r)-1-[2-(2-hydroxyethoxy)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-cyclopentyl-2-hydroxy-2-thiophen-2-ylacetate;bromide Chemical compound [Br-].C1([C@](O)(C(=O)O[C@@H]2C3CC[N+](CC3)(C2)CCOCCO)C=2SC=CC=2)CCCC1 JKLZVZUDRASWQQ-LTBDERDOSA-M 0.000 claims 1
- UMBPLDLGQHMYTD-PKMIAXOUSA-M [(3r)-1-[2-(2-hydroxyethoxy)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;chloride Chemical compound [Cl-].O([C@@H]1C2CC[N+](CC2)(C1)CCOCCO)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 UMBPLDLGQHMYTD-PKMIAXOUSA-M 0.000 claims 1
- SHOVQSPMXHNIKN-DCNLQBDOSA-M [(3r)-1-[2-(2-methoxyethoxy)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;bromide Chemical compound [Br-].O([C@@H]1C2CC[N+](CC2)(C1)CCOCCOC)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 SHOVQSPMXHNIKN-DCNLQBDOSA-M 0.000 claims 1
- DABJVNQKCHAALB-ZMDRYIOLSA-M [(3r)-1-[2-[2-(2-hydroxyethoxy)ethoxy]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CCOCCOCCO)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 DABJVNQKCHAALB-ZMDRYIOLSA-M 0.000 claims 1
- UCFILGOEDYCMDV-SPVPNRHKSA-M [(3r)-1-[3-(1,3-dioxolan-2-yl)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCCC1OCCO1 UCFILGOEDYCMDV-SPVPNRHKSA-M 0.000 claims 1
- WLXZJMCUWHRNMA-UUVFYRRLSA-M [(3r)-1-[3-(4-hydroxypiperidin-1-yl)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-cyclopentyl-2-hydroxy-2-thiophen-2-ylacetate;bromide Chemical compound [Br-].C1CC(O)CCN1CCC[N+]1(C[C@@H]2OC(=O)[C@@](O)(C3CCCC3)C=3SC=CC=3)CCC2CC1 WLXZJMCUWHRNMA-UUVFYRRLSA-M 0.000 claims 1
- CRAOAMIRGFZWMJ-LRLRVMCUSA-M [(3r)-1-[4-(4-hydroxypiperidin-1-yl)butyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2s)-2-cyclopentyl-2-hydroxy-2-thiophen-2-ylacetate;bromide Chemical compound [Br-].C1CC(O)CCN1CCCC[N+]1(C[C@@H]2OC(=O)[C@@](O)(C3CCCC3)C=3SC=CC=3)CCC2CC1 CRAOAMIRGFZWMJ-LRLRVMCUSA-M 0.000 claims 1
- YVZQKQZXKOWHPY-DMEOCDBTSA-M [(3r)-1-propan-2-yl-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)C(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 YVZQKQZXKOWHPY-DMEOCDBTSA-M 0.000 claims 1
- XAYDXTXRXYIVRQ-HFVGYZIOSA-L [Br-].C(CCCCCC)[N+]12C[C@@H](C(CC1)CC2)OC(C(C=2SC=CC2)(C=2SC=CC2)O)=O.FC(C(=O)[O-])(F)F.OC(C(=O)O[C@H]2C[N+]1(CCC2CC1)CC(C)C)(C=1SC=CC1)C=1SC=CC1 Chemical compound [Br-].C(CCCCCC)[N+]12C[C@@H](C(CC1)CC2)OC(C(C=2SC=CC2)(C=2SC=CC2)O)=O.FC(C(=O)[O-])(F)F.OC(C(=O)O[C@H]2C[N+]1(CCC2CC1)CC(C)C)(C=1SC=CC1)C=1SC=CC1 XAYDXTXRXYIVRQ-HFVGYZIOSA-L 0.000 claims 1
- MRLGSPADRUZVTC-INGGSKDUSA-L [Br-].OC1(C2=CC=CC=C2C=2C=CC=CC12)C(=O)O[C@H]1C[N+]2(CCC1CC2)CC2OC2.[Br-].C(CCCCCC)[N+]21C[C@@H](C(CC2)CC1)OC(=O)C1(C2=CC=CC=C2C=2C=CC=CC12)O Chemical compound [Br-].OC1(C2=CC=CC=C2C=2C=CC=CC12)C(=O)O[C@H]1C[N+]2(CCC1CC2)CC2OC2.[Br-].C(CCCCCC)[N+]21C[C@@H](C(CC2)CC1)OC(=O)C1(C2=CC=CC=C2C=2C=CC=CC12)O MRLGSPADRUZVTC-INGGSKDUSA-L 0.000 claims 1
- NQZQWYJMHOGQJB-RSIVIEFQSA-L [Br-].OCC[N+]12C[C@@H](C(CC1)CC2)OC(=O)C2(C1=CC=CC=C1OC=1C=CC=CC21)O.[Br-].OCC[N+]21C[C@@H](C(CC2)CC1)OC(=O)C1(C2=CC=CC=C2OC=2C=CC=CC12)O Chemical compound [Br-].OCC[N+]12C[C@@H](C(CC1)CC2)OC(=O)C2(C1=CC=CC=C1OC=1C=CC=CC21)O.[Br-].OCC[N+]21C[C@@H](C(CC2)CC1)OC(=O)C1(C2=CC=CC=C2OC=2C=CC=CC12)O NQZQWYJMHOGQJB-RSIVIEFQSA-L 0.000 claims 1
- LOCYLIDHCBHMIB-PBIWUGFPSA-L [Br-].OCC[N+]12C[C@@H](C(CC1)CC2)OC(=O)C2C1=CC=CC=C1OC=1C=CC=CC21.[Br-].C2=CC=CC=1CC3=CC=CC=C3C(C21)C(=O)O[C@H]2C[N+]1(CCC2CC1)CCO Chemical compound [Br-].OCC[N+]12C[C@@H](C(CC1)CC2)OC(=O)C2C1=CC=CC=C1OC=1C=CC=CC21.[Br-].C2=CC=CC=1CC3=CC=CC=C3C(C21)C(=O)O[C@H]2C[N+]1(CCC2CC1)CCO LOCYLIDHCBHMIB-PBIWUGFPSA-L 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- 229940100198 alkylating agent Drugs 0.000 claims 1
- 239000002168 alkylating agent Substances 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 239000005557 antagonist Substances 0.000 claims 1
- 239000000043 antiallergic agent Substances 0.000 claims 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 208000010643 digestive system disease Diseases 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- FJYCPQMVHUKUGC-SPVPNRHKSA-M ethyl 4-[(3r)-3-(2-hydroxy-2,2-dithiophen-2-ylacetyl)oxy-1-azoniabicyclo[2.2.2]octan-1-yl]butanoate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CCCC(=O)OCC)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 FJYCPQMVHUKUGC-SPVPNRHKSA-M 0.000 claims 1
- JOZJQRGYHZCPIS-WZSPKAJJSA-M ethyl 5-[(3r)-3-(2-hydroxy-2,2-dithiophen-2-ylacetyl)oxy-1-azoniabicyclo[2.2.2]octan-1-yl]pentanoate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CCCCC(=O)OCC)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 JOZJQRGYHZCPIS-WZSPKAJJSA-M 0.000 claims 1
- 208000018685 gastrointestinal system disease Diseases 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims 1
- 150000003431 steroids Chemical class 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- LODCMCANOJSMKV-ZDUSSCGKSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 2-oxo-2-phenylacetate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)C(=O)C1=CC=CC=C1 LODCMCANOJSMKV-ZDUSSCGKSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- SCEZYJKGDJPHQO-UHFFFAOYSA-M magnesium;methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=CC=C1 SCEZYJKGDJPHQO-UHFFFAOYSA-M 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- XCDQUFQBIQINAI-AIBWNMTMSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,3-diphenylpropanoate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)C(C=1C=CC=CC=1)(O)CC1=CC=CC=C1 XCDQUFQBIQINAI-AIBWNMTMSA-N 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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|---|---|---|---|
| ES200400638A ES2239546B1 (es) | 2004-03-15 | 2004-03-15 | Nuevos esteres de quinuclidina cuaternizados. |
| PCT/EP2005/002523 WO2005090342A1 (en) | 2004-03-15 | 2005-03-10 | New quaternized quinuclidine esters |
Publications (2)
| Publication Number | Publication Date |
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| JP2007529444A JP2007529444A (ja) | 2007-10-25 |
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| JP2007503242A Withdrawn JP2007529444A (ja) | 2004-03-15 | 2005-03-10 | 新しい四級化キヌクリジンエステル |
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|---|---|
| US (1) | US20080214600A1 (enExample) |
| EP (1) | EP1725552B1 (enExample) |
| JP (1) | JP2007529444A (enExample) |
| KR (1) | KR20070003940A (enExample) |
| CN (1) | CN1930158A (enExample) |
| AR (1) | AR048004A1 (enExample) |
| AT (1) | ATE399166T1 (enExample) |
| AU (1) | AU2005223310A1 (enExample) |
| BR (1) | BRPI0508177A (enExample) |
| CA (1) | CA2560157A1 (enExample) |
| CY (1) | CY1108324T1 (enExample) |
| DE (1) | DE602005007714D1 (enExample) |
| DK (1) | DK1725552T3 (enExample) |
| EC (1) | ECSP066770A (enExample) |
| ES (2) | ES2239546B1 (enExample) |
| HR (1) | HRP20080338T3 (enExample) |
| IL (1) | IL177341A0 (enExample) |
| MY (1) | MY142036A (enExample) |
| NO (1) | NO20064659L (enExample) |
| NZ (1) | NZ548583A (enExample) |
| PE (1) | PE20060005A1 (enExample) |
| PL (1) | PL1725552T3 (enExample) |
| PT (1) | PT1725552E (enExample) |
| RS (1) | RS50566B (enExample) |
| RU (1) | RU2382041C2 (enExample) |
| SI (1) | SI1725552T1 (enExample) |
| TW (1) | TW200604196A (enExample) |
| UA (1) | UA88634C2 (enExample) |
| WO (1) | WO2005090342A1 (enExample) |
| ZA (1) | ZA200605931B (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2165768B1 (es) | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
| GB0424284D0 (en) * | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
| ES2298049B1 (es) * | 2006-07-21 | 2009-10-20 | Laboratorios Almirall S.A. | Procedimiento para fabricar bromuro de 3(r)-(2-hidroxi-2,2-ditien-2-ilacetoxi)-1-(3-fenoxipropil)-1-azoniabiciclo (2.2.2) octano. |
| TW200843759A (en) * | 2007-02-15 | 2008-11-16 | Argenta Discovery Ltd | Compounds and their use II |
| WO2009035542A2 (en) | 2007-09-07 | 2009-03-19 | Theravance, Inc. | Guanidine-containing compounds useful as muscarinic receptor antagonists |
| CA2608561A1 (en) * | 2007-10-29 | 2009-04-29 | Carl Paluszkiewicz | Motorcycle wind deflector accessory support |
| US8017617B2 (en) | 2007-12-14 | 2011-09-13 | Theravance, Inc. | Amidine-containing compounds useful as muscarinic receptor antagonists |
| EP2100599A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
| EP2100598A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
| US20090326004A1 (en) | 2008-06-03 | 2009-12-31 | Ranbaxy Laboratories Limited | Muscarinic receptor antagonists |
| US20120022127A1 (en) * | 2009-04-09 | 2012-01-26 | Thomas Allmendinger | Process for preparing pyrrolidinium salts |
| EP2510928A1 (en) | 2011-04-15 | 2012-10-17 | Almirall, S.A. | Aclidinium for use in improving the quality of sleep in respiratory patients |
| CA2893663A1 (en) * | 2012-12-05 | 2014-06-12 | Chiesi Farmaceutici S.P.A. | Phenylethylpyridine derivatives as pde4-inhibitors |
| CN103755698A (zh) * | 2014-01-06 | 2014-04-30 | 万特制药(海南)有限公司 | 一锅法制备阿地溴铵的工艺 |
| CN103755699A (zh) * | 2014-01-06 | 2014-04-30 | 万特制药(海南)有限公司 | 一种2-羟基-2,2-二噻吩-2-基乙酸-1-氮杂二环[2,2,2]辛-3(r)-基酯制备方法 |
| KR101511090B1 (ko) | 2014-04-24 | 2015-04-10 | 고려대학교 산학협력단 | 염증성 질환의 예방 또는 치료용 약학 조성물 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1219606A (en) * | 1968-07-15 | 1971-01-20 | Rech S Et D Applic Scient Soge | Quinuclidinol derivatives and preparation thereof |
| US4843074A (en) * | 1988-05-17 | 1989-06-27 | Marion Laboratories, Inc. | 1-azabicyclo[2.2.2]octan-3-yl 2-aryl-3-azacyclo-2-hydroxypropionates and their quaternary salts |
| NO2005012I1 (no) * | 1994-12-28 | 2005-06-06 | Debio Rech Pharma Sa | Triptorelin og farmasoytisk akseptable salter derav |
| ES2165768B1 (es) * | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
| CA2433128C (en) * | 2000-12-28 | 2010-05-25 | Almirall Prodesfarma Ag | Novel quinuclidine derivatives and medicinal compositions containing the same |
| HUP0401849A3 (en) * | 2001-10-17 | 2007-05-02 | Ucb Sa | Quinuclidine derivatives, processes for preparing them and their uses as m2 and/or m3 muscarinic receptor inhibitors |
| ES2204295B1 (es) * | 2002-07-02 | 2005-08-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de quinuclidina-amida. |
| AR044134A1 (es) * | 2003-05-02 | 2005-08-24 | Novartis Ag | Derivados de quinuclidina, metodo de preparacion y composiciones farmaceuticas. |
-
2004
- 2004-03-15 ES ES200400638A patent/ES2239546B1/es not_active Expired - Fee Related
-
2005
- 2005-03-10 AU AU2005223310A patent/AU2005223310A1/en not_active Abandoned
- 2005-03-10 CA CA002560157A patent/CA2560157A1/en not_active Abandoned
- 2005-03-10 BR BRPI0508177-7A patent/BRPI0508177A/pt not_active IP Right Cessation
- 2005-03-10 AT AT05729711T patent/ATE399166T1/de not_active IP Right Cessation
- 2005-03-10 CN CNA2005800082369A patent/CN1930158A/zh active Pending
- 2005-03-10 KR KR1020067018902A patent/KR20070003940A/ko not_active Ceased
- 2005-03-10 JP JP2007503242A patent/JP2007529444A/ja not_active Withdrawn
- 2005-03-10 PE PE2005000281A patent/PE20060005A1/es not_active Application Discontinuation
- 2005-03-10 PT PT05729711T patent/PT1725552E/pt unknown
- 2005-03-10 PL PL05729711T patent/PL1725552T3/pl unknown
- 2005-03-10 DE DE602005007714T patent/DE602005007714D1/de not_active Expired - Lifetime
- 2005-03-10 ES ES05729711T patent/ES2307168T3/es not_active Expired - Lifetime
- 2005-03-10 DK DK05729711T patent/DK1725552T3/da active
- 2005-03-10 WO PCT/EP2005/002523 patent/WO2005090342A1/en not_active Ceased
- 2005-03-10 RS RSP-2008/0334A patent/RS50566B/sr unknown
- 2005-03-10 NZ NZ548583A patent/NZ548583A/en unknown
- 2005-03-10 US US10/592,787 patent/US20080214600A1/en not_active Abandoned
- 2005-03-10 HR HR20080338T patent/HRP20080338T3/xx unknown
- 2005-03-10 SI SI200530293T patent/SI1725552T1/sl unknown
- 2005-03-10 RU RU2006136085/04A patent/RU2382041C2/ru not_active IP Right Cessation
- 2005-03-10 EP EP05729711A patent/EP1725552B1/en not_active Expired - Lifetime
- 2005-03-11 AR ARP050100934A patent/AR048004A1/es unknown
- 2005-03-15 TW TW094107865A patent/TW200604196A/zh unknown
- 2005-03-15 MY MYPI20051090A patent/MY142036A/en unknown
- 2005-10-03 UA UAA200610595A patent/UA88634C2/ru unknown
-
2006
- 2006-07-18 ZA ZA200605931A patent/ZA200605931B/en unknown
- 2006-08-07 IL IL177341A patent/IL177341A0/en unknown
- 2006-08-14 EC EC2006006770A patent/ECSP066770A/es unknown
- 2006-10-13 NO NO20064659A patent/NO20064659L/no not_active Application Discontinuation
-
2008
- 2008-09-09 CY CY20081100965T patent/CY1108324T1/el unknown
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