FI114707B - Menetelmä terapeuttisesti käyttökelpoisten 3'-kinuklidinyyli-2-(hydroksimetyyli)-2-fenyylialkanoaattijohdannaisten valmistamiseksi ja välituote - Google Patents
Menetelmä terapeuttisesti käyttökelpoisten 3'-kinuklidinyyli-2-(hydroksimetyyli)-2-fenyylialkanoaattijohdannaisten valmistamiseksi ja välituote Download PDFInfo
- Publication number
- FI114707B FI114707B FI941170A FI941170A FI114707B FI 114707 B FI114707 B FI 114707B FI 941170 A FI941170 A FI 941170A FI 941170 A FI941170 A FI 941170A FI 114707 B FI114707 B FI 114707B
- Authority
- FI
- Finland
- Prior art keywords
- formula
- compound
- compounds
- quinuclidinyl
- preparation
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 31
- 238000000034 method Methods 0.000 title claims description 29
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 title claims description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 90
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 5
- XYPISWUKQGWYGX-UHFFFAOYSA-N 2,2,2-trifluoroethaneperoxoic acid Chemical compound OOC(=O)C(F)(F)F XYPISWUKQGWYGX-UHFFFAOYSA-N 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- -1 carbon anion Chemical class 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000004434 sulfur atom Chemical group 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 2
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims 1
- 208000006673 asthma Diseases 0.000 abstract description 3
- 229940124630 bronchodilator Drugs 0.000 abstract description 3
- 239000000168 bronchodilator agent Substances 0.000 abstract description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 abstract 1
- 230000001022 anti-muscarinic effect Effects 0.000 abstract 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
- 125000001424 substituent group Chemical group 0.000 abstract 1
- 125000001544 thienyl group Chemical group 0.000 abstract 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
- 239000000203 mixture Substances 0.000 description 27
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 21
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- 238000004458 analytical method Methods 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 239000012312 sodium hydride Substances 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 206010006482 Bronchospasm Diseases 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 210000005036 nerve Anatomy 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 230000007885 bronchoconstriction Effects 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 229920002866 paraformaldehyde Polymers 0.000 description 6
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 229930040373 Paraformaldehyde Natural products 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 229960001361 ipratropium bromide Drugs 0.000 description 5
- KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 description 5
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- IVLICPVPXWEGCA-ZETCQYMHSA-N (3r)-1-azabicyclo[2.2.2]octan-3-ol Chemical compound C1CC2[C@@H](O)CN1CC2 IVLICPVPXWEGCA-ZETCQYMHSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- 241000282326 Felis catus Species 0.000 description 4
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 4
- 229960004373 acetylcholine Drugs 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 239000013256 coordination polymer Substances 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 239000004533 oil dispersion Substances 0.000 description 4
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 4
- 230000002685 pulmonary effect Effects 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 102000017926 CHRM2 Human genes 0.000 description 3
- 241000700198 Cavia Species 0.000 description 3
- 241000700199 Cavia porcellus Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 3
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 3
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 230000008602 contraction Effects 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 210000003405 ileum Anatomy 0.000 description 3
- 230000004199 lung function Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 229960003424 phenylacetic acid Drugs 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- BLVPRHXNOPNUIH-CQSZACIVSA-N 3-[(2R)-1-azabicyclo[2.2.2]octan-2-yl]-2-phenylprop-2-enoic acid Chemical compound C1CN2CCC1C[C@@H]2C=C(C3=CC=CC=C3)C(=O)O BLVPRHXNOPNUIH-CQSZACIVSA-N 0.000 description 2
- XUHOQWJGOZLWST-UHFFFAOYSA-N 4-bromo-2-phenylbutanoic acid Chemical compound BrCCC(C(=O)O)C1=CC=CC=C1 XUHOQWJGOZLWST-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000007527 Autoreceptors Human genes 0.000 description 2
- 108010071131 Autoreceptors Proteins 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 101150012960 Chrm2 gene Proteins 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
- YMBNOESXWZMFOL-UHFFFAOYSA-N ethyl 2-(cyclohexanecarbonylamino)-6-methyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate Chemical compound S1C=2CC(C)CCC=2C(C(=O)OCC)=C1NC(=O)C1CCCCC1 YMBNOESXWZMFOL-UHFFFAOYSA-N 0.000 description 2
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 2
- QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical compound OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 230000003551 muscarinic effect Effects 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000003279 phenylacetic acid Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- KJRCEJOSASVSRA-UHFFFAOYSA-N propane-2-thiol Chemical compound CC(C)S KJRCEJOSASVSRA-UHFFFAOYSA-N 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 210000001747 pupil Anatomy 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 150000003568 thioethers Chemical class 0.000 description 2
- 210000003437 trachea Anatomy 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- SBPPWJIDARICBS-PGCXOGMSSA-N (5r,5ar,8ar,9r)-5-[[(4ar,6r,7r,8r,8as)-7,8-dihydroxy-2-phenyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4OC(OC[C@H]4O3)C=3C=CC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 SBPPWJIDARICBS-PGCXOGMSSA-N 0.000 description 1
- MYFKLQFBFSHBPA-UHFFFAOYSA-N 1-chloro-2-methylsulfanylethane Chemical compound CSCCCl MYFKLQFBFSHBPA-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- NXFFJDQHYLNEJK-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1h-cyclopenta[b]indol-3-yl]acetic acid Chemical compound C1=2C(S(=O)(=O)C)=CC(F)=CC=2C=2CCC(CC(O)=O)C=2N1CC1=CC=C(Cl)C=C1 NXFFJDQHYLNEJK-UHFFFAOYSA-N 0.000 description 1
- IUKSYUOJRHDWRR-UHFFFAOYSA-N 2-diazonio-4,6-dinitrophenolate Chemical compound [O-]C1=C([N+]#N)C=C([N+]([O-])=O)C=C1[N+]([O-])=O IUKSYUOJRHDWRR-UHFFFAOYSA-N 0.000 description 1
- ONPJWQSDZCGSQM-UHFFFAOYSA-N 2-phenylprop-2-enoic acid Chemical compound OC(=O)C(=C)C1=CC=CC=C1 ONPJWQSDZCGSQM-UHFFFAOYSA-N 0.000 description 1
- FVKFHMNJTHKMRX-UHFFFAOYSA-N 3,4,6,7,8,9-hexahydro-2H-pyrimido[1,2-a]pyrimidine Chemical compound C1CCN2CCCNC2=N1 FVKFHMNJTHKMRX-UHFFFAOYSA-N 0.000 description 1
- IVLICPVPXWEGCA-UHFFFAOYSA-N 3-quinuclidinol Chemical compound C1C[C@@H]2C(O)C[N@]1CC2 IVLICPVPXWEGCA-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- LRRFYGOWPDAWMJ-UHFFFAOYSA-N 4-ethylsulfanyl-2-phenylbutanoic acid Chemical compound CCSCCC(C(O)=O)C1=CC=CC=C1 LRRFYGOWPDAWMJ-UHFFFAOYSA-N 0.000 description 1
- XNURMQHRLYPNHZ-UHFFFAOYSA-N 4-methylsulfinyl-2-phenylbutanoic acid Chemical compound CS(=O)CCC(C(O)=O)C1=CC=CC=C1 XNURMQHRLYPNHZ-UHFFFAOYSA-N 0.000 description 1
- XAXHEFYWZJCOLL-UHFFFAOYSA-N 5-bromo-2-phenylpentanoic acid Chemical compound BrCCCC(C(=O)O)C1=CC=CC=C1 XAXHEFYWZJCOLL-UHFFFAOYSA-N 0.000 description 1
- NROITSQIVSIJEU-UHFFFAOYSA-N 5-methylsulfanyl-2-phenylpentanoic acid Chemical compound CSCCCC(C(O)=O)C1=CC=CC=C1 NROITSQIVSIJEU-UHFFFAOYSA-N 0.000 description 1
- UGMXSGJZKFDAAJ-UHFFFAOYSA-N 6-methylsulfanyl-2-phenylhexanoic acid Chemical compound CSCCCCC(C(O)=O)C1=CC=CC=C1 UGMXSGJZKFDAAJ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000009079 Bronchial Spasm Diseases 0.000 description 1
- 208000014181 Bronchial disease Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 102000017927 CHRM1 Human genes 0.000 description 1
- 102000017925 CHRM3 Human genes 0.000 description 1
- 101150060249 CHRM3 gene Proteins 0.000 description 1
- UMPJXTDHPHBSME-UHFFFAOYSA-N CSC(C)(C)CC(C(O)=O)C1=CC=CC=C1 Chemical compound CSC(C)(C)CC(C(O)=O)C1=CC=CC=C1 UMPJXTDHPHBSME-UHFFFAOYSA-N 0.000 description 1
- 244000201986 Cassia tora Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 101150073075 Chrm1 gene Proteins 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- 101000972485 Homo sapiens Lupus La protein Proteins 0.000 description 1
- 101000864782 Homo sapiens Surfactant-associated protein 2 Proteins 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 102100022742 Lupus La protein Human genes 0.000 description 1
- XOGTZOOQQBDUSI-UHFFFAOYSA-M Mesna Chemical compound [Na+].[O-]S(=O)(=O)CCS XOGTZOOQQBDUSI-UHFFFAOYSA-M 0.000 description 1
- CRZQGDNQQAALAY-UHFFFAOYSA-N Methyl benzeneacetate Chemical class COC(=O)CC1=CC=CC=C1 CRZQGDNQQAALAY-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- RSPISYXLHRIGJD-UHFFFAOYSA-N OOOO Chemical compound OOOO RSPISYXLHRIGJD-UHFFFAOYSA-N 0.000 description 1
- RSDOPYMFZBJHRL-UHFFFAOYSA-N Oxotremorine Chemical compound O=C1CCCN1CC#CCN1CCCC1 RSDOPYMFZBJHRL-UHFFFAOYSA-N 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 102100030059 Surfactant-associated protein 2 Human genes 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- CVTXNNBCSDEURM-PKOBYXMFSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] (2s)-2-(hydroxymethyl)-4-methylsulfanyl-2-phenylbutanoate Chemical compound C1([C@@](CO)(C(=O)O[C@@H]2C3CCN(CC3)C2)CCSC)=CC=CC=C1 CVTXNNBCSDEURM-PKOBYXMFSA-N 0.000 description 1
- ZFRDHSOKVYVFEI-PKOBYXMFSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] (2s)-2-(hydroxymethyl)-4-methylsulfonyl-2-phenylbutanoate Chemical compound C1([C@@](CO)(C(=O)O[C@@H]2C3CCN(CC3)C2)CCS(=O)(=O)C)=CC=CC=C1 ZFRDHSOKVYVFEI-PKOBYXMFSA-N 0.000 description 1
- DGUZNTPIFXURNF-ZVAWYAOSSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 4-ethylsulfanyl-2-phenylbutanoate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)C(CCSCC)C1=CC=CC=C1 DGUZNTPIFXURNF-ZVAWYAOSSA-N 0.000 description 1
- SZRGTZKVRMIFKI-DJNXLDHESA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 4-methylsulfanyl-2-phenylbutanoate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)C(CCSC)C1=CC=CC=C1 SZRGTZKVRMIFKI-DJNXLDHESA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 239000004855 amber Substances 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical class ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 1
- 229960004484 carbachol Drugs 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000002508 compound effect Effects 0.000 description 1
- PBGGNZZGJIKBMJ-UHFFFAOYSA-N di(propan-2-yl)azanide Chemical compound CC(C)[N-]C(C)C PBGGNZZGJIKBMJ-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- MYTMXVHNEWBFAL-UHFFFAOYSA-L dipotassium;carbonate;hydrate Chemical compound O.[K+].[K+].[O-]C([O-])=O MYTMXVHNEWBFAL-UHFFFAOYSA-L 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- QPUSANCBJDDXSA-UHFFFAOYSA-N ethanethiol;sodium Chemical compound [Na].CCS QPUSANCBJDDXSA-UHFFFAOYSA-N 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 108010020275 fibrin receptor Proteins 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000010243 gut motility Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 108091008042 inhibitory receptors Proteins 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 229960004635 mesna Drugs 0.000 description 1
- ZCCOHMPSLLIGKA-UHFFFAOYSA-N methyl 4-methylsulfanyl-2-phenylbutanoate Chemical compound CSCCC(C(=O)OC)C1=CC=CC=C1 ZCCOHMPSLLIGKA-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- UQTPDTRXCZLNRT-GMXGEUMGSA-N n-[2-[(7s)-4,7-dimethyl-3-oxo-7-bicyclo[2.2.1]heptanyl]ethyl]-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NCC[C@]1(C)C2(C)CCC1CC2=O UQTPDTRXCZLNRT-GMXGEUMGSA-N 0.000 description 1
- 230000007383 nerve stimulation Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229940124643 non-selective drug Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 210000000192 parasympathetic ganglia Anatomy 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NCAIGTHBQTXTLR-UHFFFAOYSA-N phentermine hydrochloride Chemical compound [Cl-].CC(C)([NH3+])CC1=CC=CC=C1 NCAIGTHBQTXTLR-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- ZMJJCODMIXQWCQ-UHFFFAOYSA-N potassium;di(propan-2-yl)azanide Chemical compound [K+].CC(C)[N-]C(C)C ZMJJCODMIXQWCQ-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 210000005245 right atrium Anatomy 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 238000009938 salting Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 210000003497 sciatic nerve Anatomy 0.000 description 1
- 210000002955 secretory cell Anatomy 0.000 description 1
- AIFMYMZGQVTROK-UHFFFAOYSA-N silicon tetrabromide Chemical compound Br[Si](Br)(Br)Br AIFMYMZGQVTROK-UHFFFAOYSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000004878 submucosal gland Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 210000002820 sympathetic nervous system Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/56—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pulmonology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9119705 | 1991-09-14 | ||
| GB919119705A GB9119705D0 (en) | 1991-09-14 | 1991-09-14 | Therapeutic compounds |
| EP9202067 | 1992-09-03 | ||
| PCT/EP1992/002067 WO1993006098A1 (en) | 1991-09-14 | 1992-09-03 | Quinuclidine esters process and intermediate for their preparation and pharmaceutical compositions containing them |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI941170A0 FI941170A0 (fi) | 1994-03-11 |
| FI941170L FI941170L (fi) | 1994-03-11 |
| FI114707B true FI114707B (fi) | 2004-12-15 |
Family
ID=10701448
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI941170A FI114707B (fi) | 1991-09-14 | 1994-03-11 | Menetelmä terapeuttisesti käyttökelpoisten 3'-kinuklidinyyli-2-(hydroksimetyyli)-2-fenyylialkanoaattijohdannaisten valmistamiseksi ja välituote |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US5543419A (da) |
| EP (1) | EP0603229B1 (da) |
| JP (2) | JP2672030B2 (da) |
| KR (1) | KR0135784B1 (da) |
| CN (1) | CN1037269C (da) |
| AT (1) | ATE167187T1 (da) |
| AU (1) | AU659487B2 (da) |
| BR (1) | BR9206499A (da) |
| CA (1) | CA2116356C (da) |
| CZ (1) | CZ281752B6 (da) |
| DE (1) | DE69225897T2 (da) |
| DK (1) | DK0603229T3 (da) |
| EG (1) | EG20072A (da) |
| ES (1) | ES2116343T3 (da) |
| FI (1) | FI114707B (da) |
| GB (1) | GB9119705D0 (da) |
| GR (1) | GR3027667T3 (da) |
| HU (1) | HU220594B1 (da) |
| IL (1) | IL103078A (da) |
| MX (1) | MX9205221A (da) |
| MY (1) | MY108602A (da) |
| NO (1) | NO305397B1 (da) |
| NZ (1) | NZ244324A (da) |
| PL (1) | PL170627B1 (da) |
| PT (1) | PT100863B (da) |
| RU (1) | RU2117669C1 (da) |
| SG (1) | SG50414A1 (da) |
| TW (1) | TW251285B (da) |
| UA (1) | UA42686C2 (da) |
| WO (1) | WO1993006098A1 (da) |
| ZA (1) | ZA926939B (da) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0785198T3 (da) | 1996-01-19 | 2000-11-13 | Lonza Ag | Fremgangsmåde til fremstilling af optisk aktiv 3-quinuclidinol |
| CZ54498A3 (cs) * | 1997-03-07 | 1998-11-11 | Lonza Ag | Katalyzátorová směs na bázi amorfního částečně dehydratovaného hydroxidu zirkoničitého a způsob její výroby a použití |
| US6711436B1 (en) | 1997-08-08 | 2004-03-23 | Duke University | Compositions, apparatus and methods for facilitating surgical procedures |
| WO1999007354A2 (en) * | 1997-08-08 | 1999-02-18 | Duke University | Compositions, apparatus and methods for facilitating surgical procedures |
| ES2165768B1 (es) | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
| NZ526580A (en) | 2000-12-22 | 2005-04-29 | Almirall Prodesfarma Ag | Quinuclidine carbamate derivatives and their use as M3 antagonists |
| DE60121813T2 (de) | 2000-12-28 | 2007-09-20 | Almirall Ag | Neue chinuclidinderivate und medizinische zusammensetzungen, die diese verbindungen enthalten |
| GB0424284D0 (en) * | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
| DE102004057995A1 (de) * | 2004-12-01 | 2006-06-08 | Wacker Chemie Ag | Verfahren zur Herstellung von α,α-Dialkyl-α-Hydroxymethyl-Carbonsäurederivaten |
| 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. |
| JP2010513277A (ja) * | 2006-12-13 | 2010-04-30 | ギリード・サイエンシズ・インコーポレーテッド | ＣＯＰＤおよび慢性気管支炎の治療のためのムスカリン受容体アンタゴニストおよびβ−アゴニストの共通プロドラッグとしてのモノホスフェート |
| 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 |
| EP2510928A1 (en) | 2011-04-15 | 2012-10-17 | Almirall, S.A. | Aclidinium for use in improving the quality of sleep in respiratory patients |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| GB8923590D0 (en) * | 1989-10-19 | 1989-12-06 | Pfizer Ltd | Antimuscarinic bronchodilators |
-
1991
- 1991-09-14 GB GB919119705A patent/GB9119705D0/en active Pending
-
1992
- 1992-09-03 HU HU9400729A patent/HU220594B1/hu not_active IP Right Cessation
- 1992-09-03 AU AU24823/92A patent/AU659487B2/en not_active Ceased
- 1992-09-03 AT AT92918526T patent/ATE167187T1/de not_active IP Right Cessation
- 1992-09-03 US US08/204,260 patent/US5543419A/en not_active Expired - Fee Related
- 1992-09-03 CA CA002116356A patent/CA2116356C/en not_active Expired - Fee Related
- 1992-09-03 BR BR9206499A patent/BR9206499A/pt not_active Application Discontinuation
- 1992-09-03 DK DK92918526T patent/DK0603229T3/da active
- 1992-09-03 DE DE69225897T patent/DE69225897T2/de not_active Expired - Fee Related
- 1992-09-03 CZ CS923953A patent/CZ281752B6/cs not_active IP Right Cessation
- 1992-09-03 UA UA94005520A patent/UA42686C2/uk unknown
- 1992-09-03 JP JP5505734A patent/JP2672030B2/ja not_active Expired - Fee Related
- 1992-09-03 EP EP92918526A patent/EP0603229B1/en not_active Expired - Lifetime
- 1992-09-03 PL PL92302771A patent/PL170627B1/pl unknown
- 1992-09-03 WO PCT/EP1992/002067 patent/WO1993006098A1/en not_active Ceased
- 1992-09-03 ES ES92918526T patent/ES2116343T3/es not_active Expired - Lifetime
- 1992-09-03 KR KR1019940700816A patent/KR0135784B1/ko not_active Expired - Fee Related
- 1992-09-03 RU RU94019411/04A patent/RU2117669C1/ru not_active IP Right Cessation
- 1992-09-03 SG SG1996000871A patent/SG50414A1/en unknown
- 1992-09-07 IL IL10307892A patent/IL103078A/en not_active IP Right Cessation
- 1992-09-10 TW TW081107184A patent/TW251285B/zh active
- 1992-09-11 PT PT100863A patent/PT100863B/pt active IP Right Grant
- 1992-09-11 ZA ZA926939A patent/ZA926939B/xx unknown
- 1992-09-11 MX MX9205221A patent/MX9205221A/es not_active IP Right Cessation
- 1992-09-14 MY MYPI92001642A patent/MY108602A/en unknown
- 1992-09-14 EG EG54292A patent/EG20072A/xx active
- 1992-09-14 CN CN92110746A patent/CN1037269C/zh not_active Expired - Fee Related
- 1992-09-14 NZ NZ244324A patent/NZ244324A/en unknown
-
1994
- 1994-03-11 FI FI941170A patent/FI114707B/fi not_active IP Right Cessation
- 1994-03-14 NO NO940905A patent/NO305397B1/no unknown
-
1997
- 1997-02-18 JP JP9033807A patent/JP2955533B2/ja not_active Expired - Fee Related
-
1998
- 1998-08-19 GR GR980401846T patent/GR3027667T3/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI114707B (fi) | Menetelmä terapeuttisesti käyttökelpoisten 3'-kinuklidinyyli-2-(hydroksimetyyli)-2-fenyylialkanoaattijohdannaisten valmistamiseksi ja välituote | |
| CZ20033296A3 (cs) | Benzoylsulfonamidy a sulfonylbenzamidiny jako protinádorové sloučeniny | |
| CN118290408A (zh) | 杂环化合物及其用途 | |
| SI9111647A (en) | Unsaturated hydroxyalkylquinoline acids | |
| AU593039B2 (en) | Phenoxyalkylcarboxylic acids and esters and their preparation and pharmaceutical formulation | |
| JP2012525364A5 (da) | ||
| PT1442030E (pt) | Tiofenossulfonamidas e tiazolessulfonamidas como agentes antineoplásicos | |
| JP2021501184A (ja) | Ｐ２ｘ３及び／又はｐ２ｘ２／３受容体アンタゴニスト、それを含む医薬組成物及びその使用 | |
| US20040266867A1 (en) | Novel phenylethanolamine compounds having &bgr;<sb>2</sb>acceptor excitatory function and their preparation method | |
| WO2024112895A1 (en) | Compounds and compositions for treating conditions associated with lpa receptor activity | |
| EP0150461B1 (de) | Schwefelhaltige 6-Ketoprostaglandine | |
| WO2023066359A1 (en) | Compounds and compositions for treating conditions associated with lpa receptor activity | |
| JP4826983B2 (ja) | シクロヘプタ［ｂ］ピリジン−３−カルボニルグアニジン誘導体およびそれを含有する医薬品 | |
| US20250059219A1 (en) | Lignan derivative, preparation method therefor and use thereof | |
| KR102253721B1 (ko) | 벤조티오펜 화합물 | |
| US20230339911A1 (en) | Pyridazinone compounds | |
| DK165920B (da) | Selektive biologisk aktive 7-oxo-prostacyclinderivater og fremgangsmaade til fremstilling deraf og farmaceutiske praeparater indeholdende disse | |
| HK40112914A (zh) | 用於治疗与lpa受体活性相关的病症的化合物和组合物 | |
| JP2009501723A (ja) | 抗不整脈前駆体化合物、合成方法、及び使用方法 | |
| HK40127636A (zh) | 用於治疗与lpa受体活性相关的病症的化合物和组合物 | |
| CN111138422A (zh) | 一种用于防治红斑狼疮的药物及其制备方法 | |
| HK1215570B (en) | Bensothiophene compound | |
| EP0084775A1 (de) | 13-Thia-Prostacycline |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MA | Patent expired |