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- Withdrawn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
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| 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 |
|---|---|
| JP2007529444A JP2007529444A (ja) | 2007-10-25 |
| JP2007529444A5 true JP2007529444A5 (https=) | 2008-03-21 |
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Family Applications (1)
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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 |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US20080214600A1 (https=) |
| EP (1) | EP1725552B1 (https=) |
| JP (1) | JP2007529444A (https=) |
| KR (1) | KR20070003940A (https=) |
| CN (1) | CN1930158A (https=) |
| AR (1) | AR048004A1 (https=) |
| AT (1) | ATE399166T1 (https=) |
| AU (1) | AU2005223310A1 (https=) |
| BR (1) | BRPI0508177A (https=) |
| CA (1) | CA2560157A1 (https=) |
| CY (1) | CY1108324T1 (https=) |
| DE (1) | DE602005007714D1 (https=) |
| DK (1) | DK1725552T3 (https=) |
| EC (1) | ECSP066770A (https=) |
| ES (2) | ES2239546B1 (https=) |
| HR (1) | HRP20080338T3 (https=) |
| IL (1) | IL177341A0 (https=) |
| MY (1) | MY142036A (https=) |
| NO (1) | NO20064659L (https=) |
| NZ (1) | NZ548583A (https=) |
| PE (1) | PE20060005A1 (https=) |
| PL (1) | PL1725552T3 (https=) |
| PT (1) | PT1725552E (https=) |
| RS (1) | RS50566B (https=) |
| RU (1) | RU2382041C2 (https=) |
| SI (1) | SI1725552T1 (https=) |
| TW (1) | TW200604196A (https=) |
| UA (1) | UA88634C2 (https=) |
| WO (1) | WO2005090342A1 (https=) |
| ZA (1) | ZA200605931B (https=) |
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. |
| EP2121688A1 (en) * | 2007-02-15 | 2009-11-25 | Argenta Discovery Ltd | Heterocyclic derivatives as m3 muscarinic receptors |
| JP5656288B2 (ja) | 2007-09-07 | 2015-01-21 | セラヴァンス バイオファーマ アール＆ディー アイピー， エルエルシー | ムスカリン受容体アンタゴニストとして有用なグアジニン含有化合物 |
| 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 |
| ES2617680T3 (es) * | 2009-04-09 | 2017-06-19 | Novartis Ag | Proceso para la preparación de sales de pirrolidinio |
| EP2510928A1 (en) | 2011-04-15 | 2012-10-17 | Almirall, S.A. | Aclidinium for use in improving the quality of sleep in respiratory patients |
| WO2014086852A1 (en) * | 2012-12-05 | 2014-06-12 | Chiesi Farmaceutici S.P.A. | Phenylethylpyridine derivatives as pde4-inhibitors |
| 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 |
| 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 |
| 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. |
| DE60121813T2 (de) * | 2000-12-28 | 2007-09-20 | Almirall Ag | Neue chinuclidinderivate und medizinische zusammensetzungen, die diese verbindungen enthalten |
| CN1571787A (zh) * | 2001-10-17 | 2005-01-26 | Ucb公司 | 奎宁环衍生物、制备它们的方法和它们作为m2和/或m3毒蕈碱受体抑制剂的用途 |
| 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 BR BRPI0508177-7A patent/BRPI0508177A/pt not_active IP Right Cessation
- 2005-03-10 RU RU2006136085/04A patent/RU2382041C2/ru not_active IP Right Cessation
- 2005-03-10 DE DE602005007714T patent/DE602005007714D1/de not_active Expired - Lifetime
- 2005-03-10 PE PE2005000281A patent/PE20060005A1/es not_active Application Discontinuation
- 2005-03-10 KR KR1020067018902A patent/KR20070003940A/ko not_active Ceased
- 2005-03-10 DK DK05729711T patent/DK1725552T3/da active
- 2005-03-10 SI SI200530293T patent/SI1725552T1/sl unknown
- 2005-03-10 ES ES05729711T patent/ES2307168T3/es not_active Expired - Lifetime
- 2005-03-10 US US10/592,787 patent/US20080214600A1/en not_active Abandoned
- 2005-03-10 PL PL05729711T patent/PL1725552T3/pl unknown
- 2005-03-10 EP EP05729711A patent/EP1725552B1/en not_active Expired - Lifetime
- 2005-03-10 RS RSP-2008/0334A patent/RS50566B/sr unknown
- 2005-03-10 CA CA002560157A patent/CA2560157A1/en not_active Abandoned
- 2005-03-10 AU AU2005223310A patent/AU2005223310A1/en not_active Abandoned
- 2005-03-10 CN CNA2005800082369A patent/CN1930158A/zh active Pending
- 2005-03-10 HR HR20080338T patent/HRP20080338T3/xx unknown
- 2005-03-10 NZ NZ548583A patent/NZ548583A/en unknown
- 2005-03-10 WO PCT/EP2005/002523 patent/WO2005090342A1/en not_active Ceased
- 2005-03-10 JP JP2007503242A patent/JP2007529444A/ja not_active Withdrawn
- 2005-03-10 AT AT05729711T patent/ATE399166T1/de not_active IP Right Cessation
- 2005-03-10 PT PT05729711T patent/PT1725552E/pt unknown
- 2005-03-11 AR ARP050100934A patent/AR048004A1/es unknown
- 2005-03-15 MY MYPI20051090A patent/MY142036A/en unknown
- 2005-03-15 TW TW094107865A patent/TW200604196A/zh 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
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2008
- 2008-09-09 CY CY20081100965T patent/CY1108324T1/el unknown
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