MXPA04012272A - Nuevos derivados de quinuclidina y composiciones medicinales que contienen los mismos. - Google Patents
Nuevos derivados de quinuclidina y composiciones medicinales que contienen los mismos.Info
- Publication number
- MXPA04012272A MXPA04012272A MXPA04012272A MXPA04012272A MXPA04012272A MX PA04012272 A MXPA04012272 A MX PA04012272A MX PA04012272 A MXPA04012272 A MX PA04012272A MX PA04012272 A MXPA04012272 A MX PA04012272A MX PA04012272 A MXPA04012272 A MX PA04012272A
- Authority
- MX
- Mexico
- Prior art keywords
- ylmethyl
- azoniabicyclo
- octane
- compound
- optionally substituted
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 16
- 150000008584 quinuclidines Chemical class 0.000 title 1
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 claims abstract description 12
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 239000005557 antagonist Substances 0.000 claims abstract description 4
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims abstract description 4
- -1 furan-2-ylmethyl Chemical group 0.000 claims description 440
- 150000001875 compounds Chemical class 0.000 claims description 281
- 150000002148 esters Chemical class 0.000 claims description 65
- 239000002253 acid Substances 0.000 claims description 45
- 125000001424 substituent group Chemical group 0.000 claims description 42
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 38
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
- 125000004122 cyclic group Chemical group 0.000 claims description 26
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 16
- CNWBYOPCIWGBPG-AMSMYJGSSA-N [(3r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-(3-fluorophenyl)-n-[(3,4,5-trifluorophenyl)methyl]carbamate Chemical compound FC1=CC=CC(N(CC=2C=C(F)C(F)=C(F)C=2)C(=O)O[C@@H]2C3CC[N+](CC3)(CCOC=3C=CC=CC=3)C2)=C1 CNWBYOPCIWGBPG-AMSMYJGSSA-N 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 208000023504 respiratory system disease Diseases 0.000 claims description 13
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 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 description 10
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
- 229920006395 saturated elastomer Polymers 0.000 claims description 10
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 9
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 208000014001 urinary system disease Diseases 0.000 claims description 9
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 8
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 8
- 150000001450 anions Chemical class 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 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 description 8
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 230000000241 respiratory effect Effects 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 6
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 6
- 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 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims description 5
- VQKFNUFAXTZWDK-UHFFFAOYSA-N 2-Methylfuran Chemical compound CC1=CC=CO1 VQKFNUFAXTZWDK-UHFFFAOYSA-N 0.000 claims description 4
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- 230000008485 antagonism Effects 0.000 claims description 4
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 4
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 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
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 4
- 230000006872 improvement Effects 0.000 claims description 4
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 4
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 239000000043 antiallergic agent Substances 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- AAPAVYWERMFERN-UHFFFAOYSA-N ethyl(phenyl)carbamic acid Chemical compound CCN(C(O)=O)C1=CC=CC=C1 AAPAVYWERMFERN-UHFFFAOYSA-N 0.000 claims description 3
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 150000003431 steroids Chemical class 0.000 claims description 3
- CZMKHDWWENJEBB-UHFFFAOYSA-N (2,5-dimethylfuran-3-yl)methyl-[(2-fluoro-4-methoxyphenyl)methyl]carbamic acid Chemical compound FC1=CC(OC)=CC=C1CN(C(O)=O)CC1=C(C)OC(C)=C1 CZMKHDWWENJEBB-UHFFFAOYSA-N 0.000 claims description 2
- MHHNSASWUJLGQC-UHFFFAOYSA-N (4,5-dimethylfuran-2-yl)methyl-[(5-methylfuran-2-yl)methyl]carbamic acid Chemical compound O1C(C)=CC=C1CN(C(O)=O)CC1=CC(C)=C(C)O1 MHHNSASWUJLGQC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 2
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 2
- VFCSBXIKJWAJAR-PGSWAALUSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-(3-fluorophenyl)-n-[(3-fluorophenyl)methyl]carbamate Chemical compound FC1=CC=CC(CN(C(=O)O[C@@H]2C3CC[N+](CC3)(CCCC=3C=CC=CC=3)C2)C=2C=C(F)C=CC=2)=C1 VFCSBXIKJWAJAR-PGSWAALUSA-N 0.000 claims description 2
- QFQQEWMLRDCTMK-YCQMHXFUSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-[(5-ethylthiophen-2-yl)methyl]-n-[(3-methylthiophen-2-yl)methyl]carbamate Chemical compound S1C(CC)=CC=C1CN(C(=O)O[C@@H]1C2CC[N+](CC2)(CCCC=2C=CC=CC=2)C1)CC1=C(C)C=CS1 QFQQEWMLRDCTMK-YCQMHXFUSA-N 0.000 claims description 2
- ZAPBKMWEEFIAGB-WTRWISCVSA-M [(3r)-1-heptyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-(2,5-difluorophenyl)carbamate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CCCCCCC)C(=O)N(CCCC)C1=CC(F)=CC=C1F ZAPBKMWEEFIAGB-WTRWISCVSA-M 0.000 claims description 2
- CEGCCCRGQJUBCW-BAMNPNLJSA-N [(3r)-1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-(cyclohexylmethyl)-n-(2-fluorophenyl)carbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)C)C(=O)N(C=1C(=CC=CC=1)F)CC1CCCCC1 CEGCCCRGQJUBCW-BAMNPNLJSA-N 0.000 claims description 2
- ICYPDFVERJXLOW-RBPPWHDLSA-M [(3r)-1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-(2-methylphenyl)carbamate;iodide Chemical compound [I-].CC1=CC=CC=C1N(C(=O)O[C@@H]1C2CC[N+](CC2)(C)C1)CC1=CC=CC=C1 ICYPDFVERJXLOW-RBPPWHDLSA-M 0.000 claims description 2
- DXNQLZJOTVNBOZ-UHFFFAOYSA-N [O]C(=O)Nc1ccccc1 Chemical group [O]C(=O)Nc1ccccc1 DXNQLZJOTVNBOZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 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 description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 claims description 2
- 125000003518 norbornenyl group Chemical group C12(C=CC(CC1)C2)* 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims description 2
- TVSLNRQODQRVJZ-UHFFFAOYSA-N 2-(3,4,5-trifluorophenyl)acetonitrile Chemical group FC1=CC(CC#N)=CC(F)=C1F TVSLNRQODQRVJZ-UHFFFAOYSA-N 0.000 claims 2
- 208000012931 Urologic disease Diseases 0.000 claims 2
- 208000010643 digestive system disease Diseases 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- 208000018685 gastrointestinal system disease Diseases 0.000 claims 2
- 230000001575 pathological effect Effects 0.000 claims 2
- UWFYPZAJXOAIHQ-UHFFFAOYSA-N (5-ethylthiophen-2-yl)methyl-[(3-methylthiophen-2-yl)methyl]carbamic acid Chemical compound S1C(CC)=CC=C1CN(C(O)=O)CC1=C(C)C=CS1 UWFYPZAJXOAIHQ-UHFFFAOYSA-N 0.000 claims 1
- BZYUMXXOAYSFOW-UHFFFAOYSA-N 2,3-dimethylthiophene Chemical compound CC=1C=CSC=1C BZYUMXXOAYSFOW-UHFFFAOYSA-N 0.000 claims 1
- KOVBLMNQGVQJHN-IBGZPJMESA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] n-(4-fluoro-2-methylphenyl)-n-[(3-methylthiophen-2-yl)methyl]carbamate Chemical compound C1=CSC(CN(C(=O)O[C@@H]2C3CCN(CC3)C2)C=2C(=CC(F)=CC=2)C)=C1C KOVBLMNQGVQJHN-IBGZPJMESA-N 0.000 claims 1
- IUIUVONRBVKRHR-FQEVSTJZSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] n-[2-(4-fluorophenyl)ethyl]-n-[(3-methylthiophen-2-yl)methyl]carbamate Chemical compound C1=CSC(CN(CCC=2C=CC(F)=CC=2)C(=O)O[C@@H]2C3CCN(CC3)C2)=C1C IUIUVONRBVKRHR-FQEVSTJZSA-N 0.000 claims 1
- XAKKKEVZQFSYKZ-QBJDRERVSA-M [(3r)-1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-[(4-fluorophenyl)methyl]-n-(3-methylphenyl)carbamate;iodide Chemical compound [I-].CC1=CC=CC(N(CC=2C=CC(F)=CC=2)C(=O)O[C@@H]2C3CC[N+](CC3)(C)C2)=C1 XAKKKEVZQFSYKZ-QBJDRERVSA-M 0.000 claims 1
- ZPDVAXBLZFPQPQ-QNHHWSGXSA-M [(3r)-1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-(2-fluorophenyl)carbamate;iodide Chemical compound [I-].O([C@@H]1C2CC[N+](CC2)(C1)C)C(=O)N(C=1C(=CC=CC=1)F)CC1=CC=CC=C1 ZPDVAXBLZFPQPQ-QNHHWSGXSA-M 0.000 claims 1
- 229940124748 beta 2 agonist Drugs 0.000 claims 1
- 125000001207 fluorophenyl group Chemical group 0.000 claims 1
- NCIKRCLQGDFITI-UHFFFAOYSA-N furan-3-ylmethyl-[[5-methyl-2-(trifluoromethyl)furan-3-yl]methyl]carbamic acid Chemical compound O1C(C)=CC(CN(CC2=COC=C2)C(O)=O)=C1C(F)(F)F NCIKRCLQGDFITI-UHFFFAOYSA-N 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- NVPDHMOHVWSMJD-UHFFFAOYSA-N thiophen-3-ylmethyl-[(2,4,5-trifluorophenyl)methyl]carbamic acid Chemical compound C=1C(F)=C(F)C=C(F)C=1CN(C(=O)O)CC=1C=CSC=1 NVPDHMOHVWSMJD-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 205
- 238000002360 preparation method Methods 0.000 abstract description 41
- 230000008569 process Effects 0.000 abstract description 6
- 238000002560 therapeutic procedure Methods 0.000 abstract description 3
- 150000004657 carbamic acid derivatives Chemical class 0.000 abstract description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 102
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 40
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
- KAEPUDLIBVYOEJ-XAEROCQYSA-M [(3r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-(4-fluoro-2-methylphenyl)-n-[(3-methylthiophen-2-yl)methyl]carbamate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=CSC(CN(C(=O)O[C@@H]2C3CC[N+](CC3)(CCOC=3C=CC=CC=3)C2)C=2C(=CC(F)=CC=2)C)=C1C KAEPUDLIBVYOEJ-XAEROCQYSA-M 0.000 description 32
- 239000000243 solution Substances 0.000 description 28
- 238000005481 NMR spectroscopy Methods 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- 239000003921 oil Substances 0.000 description 22
- 239000000047 product Substances 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000000725 suspension Substances 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 10
- 229910052708 sodium Inorganic materials 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 101150041968 CDC13 gene Proteins 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
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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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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Otolaryngology (AREA)
- Pain & Pain Management (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200201439A ES2203327B1 (es) | 2002-06-21 | 2002-06-21 | Nuevos carbamatos de quinuclidina y composiciones farmaceuticas que los contienen. |
| PCT/EP2003/006472 WO2004000840A2 (en) | 2002-06-21 | 2003-06-18 | Quinuclidine derivatives and pharmaceutical compositions containing the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA04012272A true MXPA04012272A (es) | 2005-04-08 |
Family
ID=29797397
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA04012272A MXPA04012272A (es) | 2002-06-21 | 2003-06-18 | Nuevos derivados de quinuclidina y composiciones medicinales que contienen los mismos. |
Country Status (21)
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1345937B1 (en) * | 2000-12-22 | 2005-09-28 | Almirall Prodesfarma AG | Quinuclidine carbamate derivatives and their use as m3 antagonists |
| ES2203327B1 (es) | 2002-06-21 | 2005-06-16 | Almirall Prodesfarma, S.A. | Nuevos carbamatos de quinuclidina y composiciones farmaceuticas que los contienen. |
| ES2204295B1 (es) | 2002-07-02 | 2005-08-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de quinuclidina-amida. |
| US7056916B2 (en) | 2002-11-15 | 2006-06-06 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Medicaments for the treatment of chronic obstructive pulmonary disease |
| EP1781298B1 (de) * | 2004-04-22 | 2012-01-04 | Boehringer Ingelheim International GmbH | Arzneinmittelkombinationen enthaltend benzoxazine zur behandlung von atemwegserkrankungen |
| WO2006005057A2 (en) * | 2004-06-30 | 2006-01-12 | Glaxo Group Limited | Muscarinic acetylcholine receptor antagonists |
| ES2246170B1 (es) * | 2004-07-29 | 2007-04-01 | Almirall Prodesfarma, S.A. | Nuevo procedimiento para preparar derivados de carbamato de quinuclidinio. |
| GB0424284D0 (en) | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
| EP1917253B1 (de) | 2005-08-15 | 2015-01-07 | Boehringer Ingelheim International Gmbh | Verfahren zur herstellung von betamimetika |
| DE102006028286A1 (de) * | 2006-06-20 | 2007-12-27 | Wirsich, Konrad, Dipl.-Ing. (FH) | Drehmoment- und rutschfest verbundene aus zwei Teilen bestehende Schaltzahnräder |
| EP1882691A1 (en) * | 2006-07-26 | 2008-01-30 | CHIESI FARMACEUTICI S.p.A. | Quinuclidine derivatives as M3 antagonists |
| WO2008096870A1 (ja) * | 2007-02-09 | 2008-08-14 | Astellas Pharma Inc. | アザ架橋環化合物 |
| KR101495708B1 (ko) * | 2007-02-23 | 2015-02-25 | 세라밴스 바이오파마 알앤디 아이피, 엘엘씨 | 무스카린 수용체 안타고니스트로 유용한 4차 암모늄 디페닐메틸 화합물 |
| EP2065385A1 (en) * | 2007-11-28 | 2009-06-03 | Laboratorios SALVAT, S.A. | Stable crystalline salt of (R)-3-fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabiciyclo [2.2.2]oct-3-yl ester |
| EP2080507A1 (en) * | 2008-01-15 | 2009-07-22 | CHIESI FARMACEUTICI S.p.A. | Pharmaceutical formulations comprising an anticholinergic drug |
| ES2655083T3 (es) * | 2010-01-28 | 2018-02-16 | Theron Pharmaceuticals, Inc. | Derivados de 7-azoniabiciclo [2.2.1]heptano, métodos de producción, y usos farmacéuticos de estos |
| LT2685986T (lt) * | 2011-03-18 | 2020-03-10 | Genzyme Corporation | Gliukozilceramido sintazės slopiklis |
| EP2631674A1 (de) * | 2012-02-23 | 2013-08-28 | ELMOS Semiconductor AG | Verfahren und Sensorsystem zur Vermessung der Eigenschaften einer Übertragungsstrecke eines Messsystems zwischen Sender und Empfänger |
| MA37975B2 (fr) | 2012-09-11 | 2021-03-31 | Genzyme Corp | Inhibiteurs de synthase de glucosylcéramide |
| RU2641285C2 (ru) * | 2013-07-13 | 2018-01-17 | Бэйцзин Фсвэлкам Текнолоджи Девелопмент Ко., Лтд | Соединения хинина, способ их получения и их медицинское применение |
| US10570127B1 (en) | 2018-11-05 | 2020-02-25 | Renexxion, Llc | Material and methods for the treatment of gastro-intestinal disorders |
| PT3920912T (pt) | 2019-02-04 | 2025-09-09 | Genzyme Corp | Tratamento de ciliopatias usando inibidores da glucosilceramida sintase (gcs) |
| IL295255A (en) | 2020-02-03 | 2022-10-01 | Genzyme Corp | Methods for treating neurological symptoms associated with lysosomal storage diseases |
| CN115605202B (zh) | 2020-03-26 | 2025-10-28 | 盐野义制药株式会社 | 具有血清素受体结合活性的芳香族杂环衍生物 |
| IL300090A (en) | 2020-07-24 | 2023-03-01 | Genzyme Corp | Pharmaceutical preparations containing VENGLUSTAT |
| WO2022145408A1 (ja) * | 2020-12-28 | 2022-07-07 | 塩野義製薬株式会社 | セロトニン受容体結合活性を有する環状アミン誘導体 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2762796A (en) * | 1956-09-11 | Iminodibenzyl derivative | ||
| GB1219606A (en) | 1968-07-15 | 1971-01-20 | Rech S Et D Applic Scient Soge | Quinuclidinol derivatives and preparation thereof |
| GB1246606A (en) | 1969-04-28 | 1971-09-15 | Starogardzkie Zakl Farma | Dibenzo-azepine derivatives |
| GB8825505D0 (en) * | 1988-11-01 | 1988-12-07 | Pfizer Ltd | Therapeutic agents |
| GB8923590D0 (en) | 1989-10-19 | 1989-12-06 | Pfizer Ltd | Antimuscarinic bronchodilators |
| GB9201751D0 (en) | 1992-01-28 | 1992-03-11 | Smithkline Beecham Plc | Compounds |
| GB9202443D0 (en) | 1992-02-05 | 1992-03-18 | Fujisawa Pharmaceutical Co | A novel substituted-acetamide compound and a process for the preparation thereof |
| AU7545894A (en) * | 1993-09-02 | 1995-03-22 | Yamanouchi Pharmaceutical Co., Ltd. | Carbamate derivative and medicine containing the same |
| AU685225B2 (en) * | 1994-02-10 | 1998-01-15 | Yamanouchi Pharmaceutical Co., Ltd. | Novel carbamate derivative and medicinal composition containing the same |
| NO2005012I1 (no) | 1994-12-28 | 2005-06-06 | Debio Rech Pharma Sa | Triptorelin og farmasoytisk akseptable salter derav |
| ATE205490T1 (de) | 1995-10-13 | 2001-09-15 | Banyu Pharma Co Ltd | Substituierte heteroaromatische derivate |
| AUPN862996A0 (en) | 1996-03-13 | 1996-04-04 | Fujisawa Pharmaceutical Co., Ltd. | A novel substituted-acetamide compound |
| PE92198A1 (es) | 1996-08-01 | 1999-01-09 | Banyu Pharma Co Ltd | Derivados de 1,4-piperidina disustituida que contienen fluor |
| ES2165768B1 (es) | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
| AU2001266100B9 (en) * | 2000-06-27 | 2005-10-06 | Laboratorios S.A.L.V.A.T., S.A. | Carbamates derived from arylalkylamines |
| EP1345937B1 (en) * | 2000-12-22 | 2005-09-28 | Almirall Prodesfarma AG | Quinuclidine carbamate derivatives and their use as m3 antagonists |
| SI1353919T1 (sl) | 2000-12-28 | 2006-12-31 | Almirall Prodesfarma Ag | Novi derivati kinuklidina in medicinske zmesi, kijih vsebujejo. |
| CA2470956C (en) * | 2001-12-20 | 2011-08-02 | Laboratorios S.A.L.V.A.T., S.A. | 1-alkyl-1-azoniabicyclo[2.2.2]octane carbamate derivatives and their use as muscarinic receptor antagonists |
| ES2203327B1 (es) | 2002-06-21 | 2005-06-16 | Almirall Prodesfarma, S.A. | Nuevos carbamatos de quinuclidina y composiciones farmaceuticas que los contienen. |
| ES2204295B1 (es) | 2002-07-02 | 2005-08-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de quinuclidina-amida. |
-
2002
- 2002-06-21 ES ES200201439A patent/ES2203327B1/es not_active Expired - Fee Related
-
2003
- 2003-06-16 UY UY27850A patent/UY27850A1/es not_active Application Discontinuation
- 2003-06-18 CA CA002490082A patent/CA2490082A1/en not_active Abandoned
- 2003-06-18 NZ NZ537252A patent/NZ537252A/en unknown
- 2003-06-18 BR BR0312169-0A patent/BR0312169A/pt not_active IP Right Cessation
- 2003-06-18 JP JP2004514785A patent/JP2005533799A/ja active Pending
- 2003-06-18 AU AU2003279384A patent/AU2003279384A1/en not_active Abandoned
- 2003-06-18 CN CNB038193272A patent/CN100363363C/zh not_active Expired - Fee Related
- 2003-06-18 PE PE2003000615A patent/PE20040579A1/es not_active Application Discontinuation
- 2003-06-18 US US10/518,496 patent/US7435742B2/en not_active Expired - Fee Related
- 2003-06-18 WO PCT/EP2003/006472 patent/WO2004000840A2/en not_active Ceased
- 2003-06-18 EP EP03740284A patent/EP1515968A2/en not_active Withdrawn
- 2003-06-18 RU RU2005101409/04A patent/RU2321588C2/ru not_active IP Right Cessation
- 2003-06-18 MX MXPA04012272A patent/MXPA04012272A/es not_active Application Discontinuation
- 2003-06-18 UA UAA200500504A patent/UA85541C2/ru unknown
- 2003-06-19 AR ARP030102175A patent/AR040275A1/es unknown
- 2003-06-20 TW TW092116832A patent/TW200401776A/zh unknown
-
2004
- 2004-12-10 EC EC2004005484A patent/ECSP045484A/es unknown
- 2004-12-15 IL IL16577504A patent/IL165775A0/xx unknown
- 2004-12-17 ZA ZA200410211A patent/ZA200410211B/xx unknown
-
2005
- 2005-01-13 NO NO20050217A patent/NO20050217L/no not_active Application Discontinuation
-
2008
- 2008-09-05 US US12/205,334 patent/US20090054480A1/en not_active Abandoned
- 2008-09-05 US US12/205,315 patent/US20090005412A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20060094751A1 (en) | 2006-05-04 |
| US20090005412A1 (en) | 2009-01-01 |
| ZA200410211B (en) | 2005-09-06 |
| WO2004000840A2 (en) | 2003-12-31 |
| RU2321588C2 (ru) | 2008-04-10 |
| IL165775A0 (en) | 2006-01-15 |
| CN100363363C (zh) | 2008-01-23 |
| US20090054480A1 (en) | 2009-02-26 |
| UY27850A1 (es) | 2003-11-28 |
| AU2003279384A1 (en) | 2004-01-06 |
| EP1515968A2 (en) | 2005-03-23 |
| ES2203327B1 (es) | 2005-06-16 |
| ECSP045484A (es) | 2005-01-28 |
| US7435742B2 (en) | 2008-10-14 |
| ES2203327A1 (es) | 2004-04-01 |
| RU2005101409A (ru) | 2005-11-20 |
| JP2005533799A (ja) | 2005-11-10 |
| NO20050217L (no) | 2005-03-18 |
| CA2490082A1 (en) | 2003-12-31 |
| TW200401776A (en) | 2004-02-01 |
| AR040275A1 (es) | 2005-03-23 |
| UA85541C2 (ru) | 2009-02-10 |
| PE20040579A1 (es) | 2004-09-08 |
| NZ537252A (en) | 2006-07-28 |
| CN1675206A (zh) | 2005-09-28 |
| WO2004000840A3 (en) | 2004-02-19 |
| BR0312169A (pt) | 2005-03-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HC | Change of company name or juridical status |
Owner name: RAUMEDIC AG |
|
| GB | Transfer or rights |
Owner name: LABORATORIOS ALMIRALL, S.A. |
|
| FA | Abandonment or withdrawal |