CA2560157A1 - New quaternized quinuclidine esters - Google Patents
New quaternized quinuclidine esters Download PDFInfo
- Publication number
- CA2560157A1 CA2560157A1 CA002560157A CA2560157A CA2560157A1 CA 2560157 A1 CA2560157 A1 CA 2560157A1 CA 002560157 A CA002560157 A CA 002560157A CA 2560157 A CA2560157 A CA 2560157A CA 2560157 A1 CA2560157 A1 CA 2560157A1
- Authority
- CA
- Canada
- 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.)
- Abandoned
Links
- 150000008584 quinuclidines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 170
- 238000000034 method Methods 0.000 claims abstract description 107
- 238000011282 treatment Methods 0.000 claims abstract description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 17
- 208000023504 respiratory system disease Diseases 0.000 claims abstract description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
- 208000018522 Gastrointestinal disease Diseases 0.000 claims abstract description 12
- 208000014001 urinary system disease Diseases 0.000 claims abstract description 12
- 230000000241 respiratory effect Effects 0.000 claims abstract description 10
- 230000008569 process Effects 0.000 claims abstract description 6
- -1 -O(CO)R1 Chemical group 0.000 claims description 135
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 11
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 10
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 7
- 208000012931 Urologic disease Diseases 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 208000010643 digestive system disease Diseases 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 208000018685 gastrointestinal system disease Diseases 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 5
- 229940100198 alkylating agent Drugs 0.000 claims description 5
- 239000002168 alkylating agent Substances 0.000 claims description 5
- 150000001450 anions Chemical class 0.000 claims description 5
- 150000001721 carbon Chemical group 0.000 claims description 5
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 238000006467 substitution reaction Methods 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 4
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 4
- 241001465754 Metazoa Species 0.000 claims description 4
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims description 4
- 239000000556 agonist Substances 0.000 claims description 4
- 239000005557 antagonist Substances 0.000 claims description 4
- 239000000043 antiallergic agent Substances 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 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 description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims description 4
- 150000003431 steroids Chemical class 0.000 claims description 4
- 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 description 3
- 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 description 3
- 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 description 3
- 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 description 3
- 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 description 3
- NDZCQVXWWZGREC-ALBCHYBFSA-M [(3r)-1-[2-(2-methoxyethoxy)ethyl]-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(CCOCCOC)CC2 NDZCQVXWWZGREC-ALBCHYBFSA-M 0.000 claims description 3
- ZNVZNTIJAFGESZ-UHFFFAOYSA-N [O-]C(C[N+]1(CCC2CC1)CC2OC(C(C1=CC=CS1)(C1=CC=CS1)O)=O)=O Chemical compound [O-]C(C[N+]1(CCC2CC1)CC2OC(C(C1=CC=CS1)(C1=CC=CS1)O)=O)=O ZNVZNTIJAFGESZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 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 3
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- GUQHKEXLVXTVRI-ZRTZFAPBSA-L C(CCCCCC)[N+]12C[C@@H](C(CC1)CC2)OC(=O)C2(C1=CC=CC=C1C=1C=CC=CC21)O.[Br-].OC2(C1=CC=CC=C1C=1C=CC=CC21)C(=O)O[C@H]2C[N+]1(CCC2CC1)CCC=C(C)C.[Br-] Chemical compound C(CCCCCC)[N+]12C[C@@H](C(CC1)CC2)OC(=O)C2(C1=CC=CC=C1C=1C=CC=CC21)O.[Br-].OC2(C1=CC=CC=C1C=1C=CC=CC21)C(=O)O[C@H]2C[N+]1(CCC2CC1)CCC=C(C)C.[Br-] GUQHKEXLVXTVRI-ZRTZFAPBSA-L 0.000 claims description 2
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 2
- LBSPHQPCEYZLST-MCOVZNOTSA-L [(3R)-1-(4-methylpent-3-enyl)-1-azoniabicyclo[2.2.2]octan-3-yl] tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaene-2-carboxylate dibromide Chemical compound [Br-].CC(=CCC[N+]12C[C@@H](C(CC1)CC2)OC(=O)C2C1=C(CCC3=C2C=CC=C3)C=CC=C1)C.[Br-].CC(=CCC[N+]13C[C@@H](C(CC1)CC3)OC(=O)C3C1=C(CCC2=C3C=CC=C2)C=CC=C1)C LBSPHQPCEYZLST-MCOVZNOTSA-L 0.000 claims description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- RGUMYJSVXRZGMN-BAGZYMAKSA-L [Br-].C1(CCCC1)[C@](C(=O)O[C@H]1C[N+]2(CCC1CC2)CCO)(C=2SC=CC2)O.[Br-].C2(CCCC2)[C@@](C(=O)O[C@H]2C[N+]1(CCC2CC1)CCO)(O)C=1SC=CC1 Chemical compound [Br-].C1(CCCC1)[C@](C(=O)O[C@H]1C[N+]2(CCC1CC2)CCO)(C=2SC=CC2)O.[Br-].C2(CCCC2)[C@@](C(=O)O[C@H]2C[N+]1(CCC2CC1)CCO)(O)C=1SC=CC1 RGUMYJSVXRZGMN-BAGZYMAKSA-L 0.000 claims description 2
- SABSUMJNAKMZOH-FHIICAAXSA-L [Br-].CC(=CCC[N+]12C[C@@H](C(CC1)CC2)OC(=O)C2C1=CC=CC=C1OC=1C=CC=CC21)C.[Br-].CC(=CCC[N+]21C[C@@H](C(CC2)CC1)OC(=O)C1C2=CC=CC=C2OC=2C=CC=CC12)C Chemical compound [Br-].CC(=CCC[N+]12C[C@@H](C(CC1)CC2)OC(=O)C2C1=CC=CC=C1OC=1C=CC=CC21)C.[Br-].CC(=CCC[N+]21C[C@@H](C(CC2)CC1)OC(=O)C1C2=CC=CC=C2OC=2C=CC=CC12)C SABSUMJNAKMZOH-FHIICAAXSA-L 0.000 claims description 2
- XCLAXVBAHKEFFB-OAMPSKHWSA-L [Br-].OC1(C2=CC=CC=C2C=2C=CC=CC12)C(=O)O[C@H]1C[N+]2(CCC1CC2)CC2OC2.[Br-].OC2(C1=CC=CC=C1C=1C=CC=CC21)C(=O)O[C@H]2C[N+]1(CCC2CC1)CC1OC1 Chemical compound [Br-].OC1(C2=CC=CC=C2C=2C=CC=CC12)C(=O)O[C@H]1C[N+]2(CCC1CC2)CC2OC2.[Br-].OC2(C1=CC=CC=C1C=1C=CC=CC21)C(=O)O[C@H]2C[N+]1(CCC2CC1)CC1OC1 XCLAXVBAHKEFFB-OAMPSKHWSA-L 0.000 claims description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 239000013066 combination product Substances 0.000 claims 2
- 229940127555 combination product Drugs 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 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
- ZFDCUNXYESQNKE-VVBMPMIJSA-L C(#N)CCC[N+]12C[C@@H](C(CC1)CC2)OC(C(C=2SC=CC2)(C=2SC=CC2)O)=O.FC(C(=O)[O-])(F)F.C(C)(=O)OCCCC[N+]21C[C@@H](C(CC2)CC1)OC(C(C=1SC=CC1)(C=1SC=CC1)O)=O.FC(C(=O)[O-])(F)F Chemical compound C(#N)CCC[N+]12C[C@@H](C(CC1)CC2)OC(C(C=2SC=CC2)(C=2SC=CC2)O)=O.FC(C(=O)[O-])(F)F.C(C)(=O)OCCCC[N+]21C[C@@H](C(CC2)CC1)OC(C(C=1SC=CC1)(C=1SC=CC1)O)=O.FC(C(=O)[O-])(F)F ZFDCUNXYESQNKE-VVBMPMIJSA-L 0.000 claims 1
- IXCGBDJBVBZNKT-BFBUHDDJSA-L FC(C(=O)[O-])(F)F.C(#N)CCCC[N+]12C[C@@H](C(CC1)CC2)OC(C(C=2SC=CC2)(C=2SC=CC2)O)=O.FC(C(=O)[O-])(F)F.C(#N)CCCC[N+]21C[C@@H](C(CC2)CC1)OC(C(O)(C=1SC=CC1)C=1SC=CC1)=O Chemical compound FC(C(=O)[O-])(F)F.C(#N)CCCC[N+]12C[C@@H](C(CC1)CC2)OC(C(C=2SC=CC2)(C=2SC=CC2)O)=O.FC(C(=O)[O-])(F)F.C(#N)CCCC[N+]21C[C@@H](C(CC2)CC1)OC(C(O)(C=1SC=CC1)C=1SC=CC1)=O IXCGBDJBVBZNKT-BFBUHDDJSA-L 0.000 claims 1
- HFMAOHJVLJKPBD-YNJOAYSNSA-L FC(C(=O)[O-])(F)F.C1(CC1)C[N+]12C[C@@H](C(CC1)CC2)OC(C(C=2SC=CC2)(C=2SC=CC2)O)=O.FC(C(=O)[O-])(F)F.C2(CC2)C[N+]21C[C@@H](C(CC2)CC1)OC(C(O)(C=1SC=CC1)C=1SC=CC1)=O Chemical compound FC(C(=O)[O-])(F)F.C1(CC1)C[N+]12C[C@@H](C(CC1)CC2)OC(C(C=2SC=CC2)(C=2SC=CC2)O)=O.FC(C(=O)[O-])(F)F.C2(CC2)C[N+]21C[C@@H](C(CC2)CC1)OC(C(O)(C=1SC=CC1)C=1SC=CC1)=O HFMAOHJVLJKPBD-YNJOAYSNSA-L 0.000 claims 1
- QXELQMNVGFEVGE-NYVZJRBMSA-L FC(C(=O)[O-])(F)F.O1C(OCC1)CC[N+]12C[C@@H](C(CC1)CC2)OC(C(C=2SC=CC2)(C=2SC=CC2)O)=O.[Br-].O2C(OCC2)CC[N+]21C[C@@H](C(CC2)CC1)OC(C(O)(C=1SC=CC1)C=1SC=CC1)=O Chemical compound FC(C(=O)[O-])(F)F.O1C(OCC1)CC[N+]12C[C@@H](C(CC1)CC2)OC(C(C=2SC=CC2)(C=2SC=CC2)O)=O.[Br-].O2C(OCC2)CC[N+]21C[C@@H](C(CC2)CC1)OC(C(O)(C=1SC=CC1)C=1SC=CC1)=O QXELQMNVGFEVGE-NYVZJRBMSA-L 0.000 claims 1
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- ODVSUCSYVTXUQA-HJOILIIGSA-L OC(C(=O)O[C@H]1C[N+]2(CCC1CC2)C(C)C)(C=2SC=CC2)C=2SC=CC2.[Br-].CC(=CCC[N+]21C[C@@H](C(CC2)CC1)OC(C(C)(C=1SC=CC1)C=1SC=CC1)=O)C.[Br-] Chemical compound OC(C(=O)O[C@H]1C[N+]2(CCC1CC2)C(C)C)(C=2SC=CC2)C=2SC=CC2.[Br-].CC(=CCC[N+]21C[C@@H](C(CC2)CC1)OC(C(C)(C=1SC=CC1)C=1SC=CC1)=O)C.[Br-] ODVSUCSYVTXUQA-HJOILIIGSA-L 0.000 claims 1
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- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000004193 piperazinyl group Chemical group 0.000 description 1
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
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- 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
- A61K31/435—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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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Heart & Thoracic Surgery (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Otolaryngology (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200400638A ES2239546B1 (es) | 2004-03-15 | 2004-03-15 | Nuevos esteres de quinuclidina cuaternizados. |
| ESP200400638 | 2004-03-15 | ||
| PCT/EP2005/002523 WO2005090342A1 (en) | 2004-03-15 | 2005-03-10 | New quaternized quinuclidine esters |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2560157A1 true CA2560157A1 (en) | 2005-09-29 |
Family
ID=34955916
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002560157A Abandoned CA2560157A1 (en) | 2004-03-15 | 2005-03-10 | New quaternized quinuclidine esters |
Country Status (30)
| Country | Link |
|---|---|
| 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. |
| MX2009008323A (es) * | 2007-02-15 | 2009-08-13 | Argenta Discovery Ltd | Derivados heterociclicos como receptores muscarinicos m3. |
| BRPI0816219B8 (pt) | 2007-09-07 | 2021-05-25 | Theravance Biopharma R&D Ip Llc | compostos contendo guanidina úteis como antagonistas de receptor muscarínico, composição farmacêutica e uso |
| CA2608561A1 (en) * | 2007-10-29 | 2009-04-29 | Carl Paluszkiewicz | Motorcycle wind deflector accessory support |
| EP2222637A1 (en) | 2007-12-14 | 2010-09-01 | 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 |
| JP5902612B2 (ja) | 2009-04-09 | 2016-04-13 | ノバルティス アーゲー | ピロリジニウム塩の調製方法 |
| EP2510928A1 (en) | 2011-04-15 | 2012-10-17 | Almirall, S.A. | Aclidinium for use in improving the quality of sleep in respiratory patients |
| HK1212986A1 (zh) * | 2012-12-05 | 2016-06-24 | 奇斯药制品公司 | 作为pde4-抑制剂的苯基乙基吡啶衍生物 |
| 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. |
| KR100869721B1 (ko) * | 2000-12-28 | 2008-11-21 | 알미랄 에이쥐 | 신규한 퀴누클리딘 유도체 및 그를 함유한 의약 조성물 |
| EP1438309A1 (en) * | 2001-10-17 | 2004-07-21 | Ucb, S.A. | 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 RS RSP-2008/0334A patent/RS50566B/sr unknown
- 2005-03-10 PT PT05729711T patent/PT1725552E/pt unknown
- 2005-03-10 ES ES05729711T patent/ES2307168T3/es not_active Expired - Lifetime
- 2005-03-10 DK DK05729711T patent/DK1725552T3/da active
- 2005-03-10 CN CNA2005800082369A patent/CN1930158A/zh active Pending
- 2005-03-10 PE PE2005000281A patent/PE20060005A1/es not_active Application Discontinuation
- 2005-03-10 US US10/592,787 patent/US20080214600A1/en not_active Abandoned
- 2005-03-10 BR BRPI0508177-7A patent/BRPI0508177A/pt not_active IP Right Cessation
- 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 AU AU2005223310A patent/AU2005223310A1/en not_active Abandoned
- 2005-03-10 PL PL05729711T patent/PL1725552T3/pl unknown
- 2005-03-10 KR KR1020067018902A patent/KR20070003940A/ko not_active Ceased
- 2005-03-10 AT AT05729711T patent/ATE399166T1/de not_active IP Right Cessation
- 2005-03-10 NZ NZ548583A patent/NZ548583A/en unknown
- 2005-03-10 JP JP2007503242A patent/JP2007529444A/ja not_active Withdrawn
- 2005-03-10 WO PCT/EP2005/002523 patent/WO2005090342A1/en not_active Ceased
- 2005-03-10 EP EP05729711A patent/EP1725552B1/en not_active Expired - Lifetime
- 2005-03-10 HR HR20080338T patent/HRP20080338T3/xx unknown
- 2005-03-10 CA CA002560157A patent/CA2560157A1/en not_active Abandoned
- 2005-03-10 DE DE602005007714T patent/DE602005007714D1/de 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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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |