IL87643A - Thiazoles, their preparation and pharmaceutical preparations containing them - Google Patents
Thiazoles, their preparation and pharmaceutical preparations containing themInfo
- Publication number
- IL87643A IL87643A IL8764388A IL8764388A IL87643A IL 87643 A IL87643 A IL 87643A IL 8764388 A IL8764388 A IL 8764388A IL 8764388 A IL8764388 A IL 8764388A IL 87643 A IL87643 A IL 87643A
- Authority
- IL
- Israel
- Prior art keywords
- thiadiazol
- methyl
- tetrahydropyridine
- azabicyclo
- alkyl
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 7
- 150000004867 thiadiazoles Chemical class 0.000 title abstract description 22
- 150000001875 compounds Chemical class 0.000 claims abstract description 134
- 125000001424 substituent group Chemical group 0.000 claims abstract description 23
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 22
- 125000003118 aryl group Chemical group 0.000 claims abstract description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 6
- 230000000926 neurological effect Effects 0.000 claims abstract description 4
- 208000020016 psychiatric disease Diseases 0.000 claims abstract description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract 7
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 57
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 55
- 238000000034 method Methods 0.000 claims description 47
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 36
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 claims description 35
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 30
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical group 0.000 claims description 16
- 239000000651 prodrug Substances 0.000 claims description 15
- 229940002612 prodrug Drugs 0.000 claims description 15
- -1 hydroxy, carboxy Chemical group 0.000 claims description 13
- 150000002431 hydrogen Chemical group 0.000 claims description 12
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 claims description 6
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 239000000812 cholinergic antagonist Substances 0.000 claims description 6
- 150000002825 nitriles Chemical class 0.000 claims description 6
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 5
- IBANRDPEOYZVGW-UHFFFAOYSA-N 3-methyl-1,2,4-thiadiazole Chemical compound CC=1N=CSN=1 IBANRDPEOYZVGW-UHFFFAOYSA-N 0.000 claims description 4
- IVLICPVPXWEGCA-UHFFFAOYSA-N 3-quinuclidinol Chemical compound C1C[C@@H]2C(O)C[N@]1CC2 IVLICPVPXWEGCA-UHFFFAOYSA-N 0.000 claims description 4
- 150000001450 anions Chemical class 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000002093 peripheral effect Effects 0.000 claims description 4
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 4
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 4
- KPUSZZFAYGWAHZ-UHFFFAOYSA-N 3-azabicyclo[2.2.2]octane Chemical compound C1CC2CCC1NC2 KPUSZZFAYGWAHZ-UHFFFAOYSA-N 0.000 claims description 3
- 208000012902 Nervous system disease Diseases 0.000 claims description 3
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 238000006352 cycloaddition reaction Methods 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- IECBFBGUELVRBA-UHFFFAOYSA-N n,n-dimethyl-1,2,4-thiadiazol-3-amine Chemical compound CN(C)C=1N=CSN=1 IECBFBGUELVRBA-UHFFFAOYSA-N 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- FWMUJAIKEJWSSY-UHFFFAOYSA-N sulfur dichloride Chemical compound ClSCl FWMUJAIKEJWSSY-UHFFFAOYSA-N 0.000 claims description 3
- VTGXCBWCWSIASR-UHFFFAOYSA-N 3-cyclopropyl-1,2,4-thiadiazole Chemical compound C1CC1C1=NSC=N1 VTGXCBWCWSIASR-UHFFFAOYSA-N 0.000 claims description 2
- 230000018044 dehydration Effects 0.000 claims description 2
- 238000006297 dehydration reaction Methods 0.000 claims description 2
- 150000004985 diamines Chemical class 0.000 claims description 2
- BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- ADRDEXBBJTUCND-UHFFFAOYSA-N pyrrolizidine Chemical compound C1CCN2CCCC21 ADRDEXBBJTUCND-UHFFFAOYSA-N 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
- AMPSNBFBYWOSQO-UHFFFAOYSA-N 3-benzyl-1,2,4-thiadiazole Chemical compound C=1C=CC=CC=1CC=1N=CSN=1 AMPSNBFBYWOSQO-UHFFFAOYSA-N 0.000 claims 2
- 208000025966 Neurological disease Diseases 0.000 claims 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 1
- LKAYAMCKQCBSOU-UHFFFAOYSA-N 3-chloro-1,2,4-thiadiazole Chemical compound ClC=1N=CSN=1 LKAYAMCKQCBSOU-UHFFFAOYSA-N 0.000 claims 1
- PDRIOPYWJATUTD-UHFFFAOYSA-N 3-ethyl-1,2,4-thiadiazole Chemical compound CCC=1N=CSN=1 PDRIOPYWJATUTD-UHFFFAOYSA-N 0.000 claims 1
- PAPIULIUHITHDW-UHFFFAOYSA-N 3-phenyl-1,2,4-thiadiazole Chemical compound S1C=NC(C=2C=CC=CC=2)=N1 PAPIULIUHITHDW-UHFFFAOYSA-N 0.000 claims 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
- 239000000472 muscarinic agonist Substances 0.000 abstract description 3
- 230000008901 benefit Effects 0.000 abstract description 2
- 230000003389 potentiating effect Effects 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 210
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 147
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 103
- 239000000243 solution Substances 0.000 description 90
- 239000012458 free base Substances 0.000 description 70
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 59
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 54
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 42
- 239000000203 mixture Substances 0.000 description 38
- MUBZPKHOEPUJKR-UHFFFAOYSA-M oxalate(1-) Chemical compound OC(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-M 0.000 description 35
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 32
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 30
- 239000002904 solvent Substances 0.000 description 30
- 239000000284 extract Substances 0.000 description 29
- 238000006243 chemical reaction Methods 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- 229960004132 diethyl ether Drugs 0.000 description 27
- 239000003921 oil Substances 0.000 description 27
- 235000019198 oils Nutrition 0.000 description 27
- 101150041968 CDC13 gene Proteins 0.000 description 26
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- 229910000027 potassium carbonate Inorganic materials 0.000 description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- 239000007787 solid Substances 0.000 description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 17
- 239000007864 aqueous solution Substances 0.000 description 15
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 15
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 15
- 235000006408 oxalic acid Nutrition 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 13
- 238000002425 crystallisation Methods 0.000 description 13
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- 239000000377 silicon dioxide Substances 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 10
- 150000002430 hydrocarbons Chemical group 0.000 description 10
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- HAKSOKWVNPZVNM-UHFFFAOYSA-N 1,2,3,4-tetrahydropyridine;hydrochloride Chemical compound Cl.C1CNC=CC1 HAKSOKWVNPZVNM-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 239000012298 atmosphere Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 208000024827 Alzheimer disease Diseases 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
- 150000002576 ketones Chemical group 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 229920002261 Corn starch Polymers 0.000 description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- 239000008120 corn starch Substances 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- RSOWDTALVBLZPE-UHFFFAOYSA-N methyl 1-azabicyclo[2.2.2]octane-3-carboxylate Chemical compound C1CC2C(C(=O)OC)CN1CC2 RSOWDTALVBLZPE-UHFFFAOYSA-N 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 229960001866 silicon dioxide Drugs 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 4
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 4
- 150000005690 diesters Chemical class 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000007429 general method Methods 0.000 description 4
- NQYKOGPMIBDYAS-UHFFFAOYSA-N heptane;oxalic acid Chemical compound OC(=O)C(O)=O.CCCCCCC NQYKOGPMIBDYAS-UHFFFAOYSA-N 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- YTJXGDYAEOTOCG-UHFFFAOYSA-N lithium;di(propan-2-yl)azanide;oxolane Chemical compound [Li+].C1CCOC1.CC(C)[N-]C(C)C YTJXGDYAEOTOCG-UHFFFAOYSA-N 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- LVBCACDXSOCLCG-UHFFFAOYSA-N methyl 1-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound C1CC2C(C(=O)OC)CN1C2 LVBCACDXSOCLCG-UHFFFAOYSA-N 0.000 description 4
- WJHZOWPRNOSKTK-UHFFFAOYSA-N octane;oxalic acid Chemical compound OC(=O)C(O)=O.CCCCCCCC WJHZOWPRNOSKTK-UHFFFAOYSA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- BZBPZAIVJSSELJ-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octane;oxalic acid Chemical compound OC(=O)C(O)=O.C1CC2CCN1CC2 BZBPZAIVJSSELJ-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 125000006519 CCH3 Chemical group 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 3
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- DQPBABKTKYNPMH-UHFFFAOYSA-N amino hydrogen sulfate Chemical compound NOS(O)(=O)=O DQPBABKTKYNPMH-UHFFFAOYSA-N 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 230000001713 cholinergic effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000003551 muscarinic effect Effects 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000001117 sulphuric acid Substances 0.000 description 3
- 235000011149 sulphuric acid Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000016978 synaptic transmission, cholinergic Effects 0.000 description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- FBZVZUSVGKOWHG-UHFFFAOYSA-N 1,1-dimethoxy-n,n-dimethylethanamine Chemical compound COC(C)(OC)N(C)C FBZVZUSVGKOWHG-UHFFFAOYSA-N 0.000 description 2
- JVCBVWTTXCNJBJ-UHFFFAOYSA-N 1-azabicyclo[2.2.1]heptane Chemical compound C1CC2CCN1C2 JVCBVWTTXCNJBJ-UHFFFAOYSA-N 0.000 description 2
- SOYISIZZTHPRSO-UHFFFAOYSA-N 4-pyridin-2-ylthiadiazole Chemical compound S1N=NC(C=2N=CC=CC=2)=C1 SOYISIZZTHPRSO-UHFFFAOYSA-N 0.000 description 2
- AWBVSQNEHPVFIF-UHFFFAOYSA-N 5-chloro-3-propan-2-yl-1,2,4-thiadiazole Chemical compound CC(C)C1=NSC(Cl)=N1 AWBVSQNEHPVFIF-UHFFFAOYSA-N 0.000 description 2
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- ZWWQRMFIZFPUAA-UHFFFAOYSA-N dimethyl 2-methylidenebutanedioate Chemical compound COC(=O)CC(=C)C(=O)OC ZWWQRMFIZFPUAA-UHFFFAOYSA-N 0.000 description 1
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- MPEUOPWWEODARH-UHFFFAOYSA-N ethyl pyrrolidine-3-carboxylate Chemical compound CCOC(=O)C1CCNC1 MPEUOPWWEODARH-UHFFFAOYSA-N 0.000 description 1
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- ZIUUUKKAMFKVCY-UHFFFAOYSA-N methyl 3-azabicyclo[2.2.2]octane-5-carboxylate Chemical compound C1CC2C(C(=O)OC)CC1CN2 ZIUUUKKAMFKVCY-UHFFFAOYSA-N 0.000 description 1
- MDFRYRPNRLLJHT-UHFFFAOYSA-N methyl carbamimidate;sulfuric acid Chemical compound COC(N)=N.OS(O)(=O)=O MDFRYRPNRLLJHT-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- BCDBHIAXYFPJCT-UHFFFAOYSA-N methyl piperidine-3-carboxylate Chemical compound COC(=O)C1CCCNC1 BCDBHIAXYFPJCT-UHFFFAOYSA-N 0.000 description 1
- VVWWZOKQKXPVIV-UHFFFAOYSA-N methyl pyrrolidine-3-carboxylate Chemical compound COC(=O)C1CCNC1 VVWWZOKQKXPVIV-UHFFFAOYSA-N 0.000 description 1
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- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
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- 239000012038 nucleophile Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- HALBYYBBCLBMJB-UHFFFAOYSA-N oxalic acid;pyrrolidine Chemical compound C1CCNC1.OC(=O)C(O)=O HALBYYBBCLBMJB-UHFFFAOYSA-N 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
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- RPMPUBPKEIONCM-UHFFFAOYSA-N phenyl(1,2,4-thiadiazol-3-yl)methanol Chemical compound C=1C=CC=CC=1C(O)C=1N=CSN=1 RPMPUBPKEIONCM-UHFFFAOYSA-N 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
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- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
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- 239000002244 precipitate Substances 0.000 description 1
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- 230000002035 prolonged effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 229960000697 propantheline Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridine hydrochloride Substances [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
- XQWBMZWDJAZPPX-UHFFFAOYSA-N pyridine-3-carbothioamide Chemical compound NC(=S)C1=CC=CN=C1 XQWBMZWDJAZPPX-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 239000004296 sodium metabisulphite Substances 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 150000005691 triesters Chemical class 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000016776 visual perception Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/06—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing isoquinuclidine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Cephalosporin Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB878721342A GB8721342D0 (en) | 1987-09-10 | 1987-09-10 | Therapeutic agents |
| GB888801758A GB8801758D0 (en) | 1988-01-27 | 1988-01-27 | Therapeutic agents |
| GB888812145A GB8812145D0 (en) | 1988-05-23 | 1988-05-23 | Therapeutic agents |
| GB888817311A GB8817311D0 (en) | 1988-07-20 | 1988-07-20 | Therapeutic agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL87643A0 IL87643A0 (en) | 1989-02-28 |
| IL87643A true IL87643A (en) | 1994-05-30 |
Family
ID=27449981
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL8764388A IL87643A (en) | 1987-09-10 | 1988-09-01 | Thiazoles, their preparation and pharmaceutical preparations containing them |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP0307142B1 (de) |
| JP (1) | JPH01104070A (de) |
| KR (1) | KR890005103A (de) |
| AT (1) | ATE111464T1 (de) |
| AU (1) | AU626209B2 (de) |
| DE (1) | DE3851498T2 (de) |
| DK (1) | DK503188A (de) |
| IL (1) | IL87643A (de) |
| NZ (1) | NZ225999A (de) |
| PT (1) | PT88422B (de) |
Families Citing this family (66)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0287356B1 (de) * | 1987-04-15 | 1996-01-24 | Beecham Group Plc | Am Brückenkopf substituierte Azabicyclenderivate |
| CA2000041A1 (en) * | 1988-10-13 | 1990-04-13 | Barry S. Orlek | Compounds |
| GB8830226D0 (en) * | 1988-12-23 | 1989-02-22 | Beecham Group Plc | Novel compounds |
| US5260311A (en) * | 1989-02-22 | 1993-11-09 | Novo Nordisk A/S | Piperidine compounds and their use |
| US5328925A (en) * | 1989-02-22 | 1994-07-12 | Novo Nordisk A/S | Piperidine compounds and their use |
| US5043345A (en) * | 1989-02-22 | 1991-08-27 | Novo Nordisk A/S | Piperidine compounds and their preparation and use |
| US5264444A (en) * | 1989-02-22 | 1993-11-23 | Novo Nordisk A/S | Piperidine compounds and use |
| US5106853A (en) * | 1989-05-15 | 1992-04-21 | Merck Sharp & Dohme, Ltd. | Oxadiazole and its salts, their use in treating dementia |
| ATE153024T1 (de) * | 1989-08-16 | 1997-05-15 | Beecham Group Plc | Azabicyclische verbindungen |
| DE69026197T2 (de) * | 1989-10-07 | 1997-01-09 | Beecham Group Plc | Azabizyklische Verbindungen, Verfahren und Zwischenprodukte zu ihrer Herstellung und diese enthaltende pharmazeutische Zubereitungen |
| EP0459568A3 (en) * | 1990-05-31 | 1992-09-30 | Merck Sharp & Dohme Ltd. | Substituted oxadiazoles and thiadiazoles for use in the treatment of glaucoma and novel compounds having such use |
| DK198490D0 (da) * | 1990-08-21 | 1990-08-21 | Novo Nordisk As | Heterocykliske forbindelser, deres fremstilling og anvendelse |
| DK198590D0 (da) * | 1990-08-21 | 1990-08-21 | Novo Nordisk As | Heterocykliske forbindelser, deres fremstilling og anvendelse |
| US5418240A (en) * | 1990-08-21 | 1995-05-23 | Novo Nordisk A/S | Heterocyclic compounds and their preparation and use |
| DK198390D0 (da) * | 1990-08-21 | 1990-08-21 | Novo Nordisk As | Heterocykliske forbindelser, deres fremstilling og anvendelse |
| US5376668A (en) * | 1990-08-21 | 1994-12-27 | Novo Nordisk A/S | Heterocyclic compounds |
| US5527813A (en) * | 1990-08-21 | 1996-06-18 | Novo Nordisk A/S | Heterocyclic compounds and their preparation and use |
| US5124460A (en) * | 1991-05-06 | 1992-06-23 | Merck Sharp & Dohme Ltd. | Enantioselective synthesis of 3-substituted 1-azabicyclo (2.2.1)heptanes |
| US5641791A (en) * | 1991-08-13 | 1997-06-24 | Novo Nordisk A.S | Heterocyclic compounds and their preparation and use |
| GB9127279D0 (en) * | 1991-12-23 | 1992-02-19 | Ici Plc | Heterocyclic derivatives |
| WO1993014089A1 (en) * | 1992-01-13 | 1993-07-22 | Novo Nordisk A/S | Heterocyclic compounds and their preparation and use |
| JPH06508377A (ja) * | 1992-04-10 | 1994-09-22 | ゼネカ リミテッド | ヘテロ環式化合物 |
| SE9201478D0 (sv) * | 1992-05-11 | 1992-05-11 | Kabi Pharmacia Ab | Heteroaromatic quinuclidinenes, their use and preparation |
| GB9211796D0 (en) * | 1992-06-04 | 1992-07-15 | Ici Plc | Heterocyclic derivatives |
| GB9216721D0 (en) * | 1992-08-06 | 1992-09-23 | Ici Plc | Therapeutic heterocyclic derivatives |
| GB9218334D0 (en) * | 1992-08-28 | 1992-10-14 | Ici Plc | Heterocyclic compounds |
| GB9226573D0 (en) * | 1992-12-21 | 1993-02-17 | Ici Plc | Heterocyclic compounds |
| WO1994014803A1 (en) * | 1992-12-21 | 1994-07-07 | Zeneca Limited | Quinuclidine derivatives as squalene synthase inhibitors |
| KR100360575B1 (ko) * | 1993-08-19 | 2003-03-10 | 노보 노르디스크 에이/에스 | 정신분열증및정신분열형질환치료용약제학적조성물 |
| US5753683A (en) * | 1993-08-19 | 1998-05-19 | Novo Nordisk A/S | Antipsychotic method |
| US6265419B1 (en) | 1993-12-21 | 2001-07-24 | Novo Nordisk A/S | Method of treating gastrointestinal motility disorders |
| US6281232B1 (en) | 1993-08-19 | 2001-08-28 | Novo Nordisk A/S | Method of treating gastrointestinal motility disorders |
| US5545638A (en) * | 1993-12-21 | 1996-08-13 | Novo Nordisk A/S | Method of treating gastrointestinal motility disorders |
| IL112024A (en) * | 1993-12-21 | 1999-07-14 | Novo Nordisk As | Pharmaceutical compositions comprising tetrahydropyridine derivatives substituted with oxadiazole or thiadiazole for treating gastrointestinal motility disorders |
| US5646289A (en) * | 1994-10-24 | 1997-07-08 | Eli Lilly And Company | Heterocyclic compounds and their preparation and use |
| US5565475A (en) * | 1994-11-08 | 1996-10-15 | Muhlhauser; Mark A. | Method of treating urinary bladder dysfunctions with 3-tetrahydropyridine derivatives |
| US5612351A (en) * | 1994-11-08 | 1997-03-18 | Novo Nordisk A/S | Method of treating urinary bladder dysfunctions |
| US5510478A (en) * | 1994-11-30 | 1996-04-23 | American Home Products Corporation | 2-arylamidothiazole derivatives with CNS activity |
| US5859004A (en) * | 1995-02-17 | 1999-01-12 | Novo Nordisk A/S | Use of heterocyclic compounds for the treatment of conditions caused by malfunctioning of the nicotinic cholinergic system |
| GB9510459D0 (en) * | 1995-05-24 | 1995-07-19 | Zeneca Ltd | Bicyclic amines |
| US5712270A (en) * | 1995-11-06 | 1998-01-27 | American Home Products Corporation | 2-arylamidothiazole derivatives with CNS activity |
| AU1141497A (en) * | 1995-11-29 | 1997-06-19 | Eli Lilly And Company | Heterocyclic compounds and their use |
| US5889019A (en) * | 1995-11-29 | 1999-03-30 | Eli Lilly And Company | Heterocyclic compounds and their use |
| EP0871445A4 (de) * | 1995-12-07 | 2001-01-10 | Lilly Co Eli | Mittel zur schmerzbehandlung |
| US5914338A (en) * | 1996-04-02 | 1999-06-22 | Novo Nordisk | Heterocyclic compounds and their preparation and use |
| AU2568597A (en) * | 1996-04-24 | 1997-11-12 | Novo Nordisk A/S | Heterocyclic compounds and their preparation and use |
| WO1997043286A1 (en) * | 1996-05-13 | 1997-11-20 | Zeneca Limited | Bicyclic amines as insecticides |
| US6090829A (en) * | 1996-08-01 | 2000-07-18 | Eli Lilly And Company | Method for treating excessive aggression |
| US6117890A (en) * | 1996-08-01 | 2000-09-12 | Eli Lilly And Company | Method for treating bipolar disorder |
| EP0821956A1 (de) * | 1996-08-01 | 1998-02-04 | Eli Lilly And Company | Verfahren zur Behandlung disruptiver Verhaltensstörungen |
| EP0821954A1 (de) * | 1996-08-01 | 1998-02-04 | Eli Lilly And Company | Verfahren zur Behandlung von geistiger Zurückgebliebenheit |
| US6043258A (en) * | 1996-08-01 | 2000-03-28 | Eli Lilly And Company | Method for treating disruptive behavior disorders with xanomeline |
| US5834458A (en) * | 1996-10-09 | 1998-11-10 | Eli Lilly And Company | Heterocyclic compounds and their use |
| GB9623944D0 (en) * | 1996-11-15 | 1997-01-08 | Zeneca Ltd | Bicyclic amine derivatives |
| GB9624114D0 (en) * | 1996-11-20 | 1997-01-08 | Zeneca Ltd | Pesticidal bicyclic amine derivatives |
| WO1998025924A1 (en) | 1996-11-26 | 1998-06-18 | Zeneca Limited | 8-azabicyclo[3.2.1]octane-, 8-azabicyclo[3.2.1]oct-6-ene-, 9-azabicyclo[3.3.1]nonane-, 9-aza-3-oxabicyclo[3.3.1]nonane- and 9-aza-3-thiabicyclo[3.3.1]nonane derivatives, their preparation and their use as insecticides |
| GB9624611D0 (en) * | 1996-11-26 | 1997-01-15 | Zeneca Ltd | Bicyclic amine compounds |
| US5733912A (en) * | 1997-02-19 | 1998-03-31 | Abbott Laboratories | 7A-heterocycle substituted hexahydro-1H-pyrrolizine compounds useful in controlling chemical synaptic transmission |
| US6034108A (en) * | 1997-07-28 | 2000-03-07 | Eli Lilly And Company | Method for treating mental retardation |
| US7332508B2 (en) * | 2002-12-18 | 2008-02-19 | Novo Nordisk A/S | Substituted homopiperidine, piperidine or pyrrolidine derivatives |
| RS53981B1 (sr) | 2006-03-24 | 2015-10-30 | Array Biopharma Inc. | Analozi 2-aminopiridina kao aktivatori glukokinaze |
| KR20090110353A (ko) * | 2007-02-15 | 2009-10-21 | 아젠터 디스커버리 리미티드 | Ｍ３ 무스카린 수용체로서의 헤테로시클릭 유도체 |
| JP2008270387A (ja) * | 2007-04-18 | 2008-11-06 | Matsushita Electric Ind Co Ltd | プリント配線板 |
| EP2072506A1 (de) * | 2007-12-21 | 2009-06-24 | Bayer CropScience AG | Thiazolyloxyphenylamidine oder Thiadiazolyloxyphenylamidine und deren Verwendung als Fungizide |
| US20110294835A1 (en) | 2008-05-15 | 2011-12-01 | The Board Of Trustees Of The University Of Illinois | Muscarinic Agonists as Cognitive Enhancers |
| US9549928B2 (en) | 2011-04-29 | 2017-01-24 | The University Of Toledo | Muscarinic agonists as enhancers of cognitive flexibility |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3770749A (en) * | 1971-07-01 | 1973-11-06 | Monsanto Co | 3-pyridyl-1,2,4-thiadiazole-5-carboxamides |
| BE789441A (fr) * | 1971-09-30 | 1973-03-29 | Ciba Geigy | Nouvel herbicide selectif et procede pour sa preparation |
| US4226609A (en) * | 1979-03-01 | 1980-10-07 | Olin Corporation | Selected 3-trichloromethyl-5-cyclic amine-1,2,4-thiadiazole compounds and their use as ammonium nitrification inhibitors |
| EP0018497B1 (de) * | 1979-04-06 | 1982-04-28 | Bayer Ag | Azolyloxy-essigsäureamide, Verfahren zu ihrer Herstellung und ihre Verwendung als Herbizide |
| US4282144A (en) * | 1979-06-01 | 1981-08-04 | Eastman Kodak Company | Azo dyes derived from 5-membered heterocyclic amines and aromatic amine couplers containing sulfo groups, or salts thereof |
| US4301069A (en) * | 1980-06-13 | 1981-11-17 | Eastman Kodak Company | Azo dyes from five membered ring heterocyclic amines and aniline, tetrahydroquinoline and benzomorpholine couplers containing thiosulfate alkyl groups |
| DE3038636A1 (de) * | 1980-10-13 | 1982-05-27 | Bayer Ag, 5090 Leverkusen | Verfahren zur herstellung von substituierten oxyessigsaeureamiden |
| DE3422861A1 (de) * | 1984-06-20 | 1986-01-02 | Bayer Ag, 5090 Leverkusen | Verfahren zur herstellung von heteroaryloxyacetamiden |
| NZ219646A (en) * | 1986-03-27 | 1990-10-26 | Merck Sharp & Dohme | Oxadiazole derivatives of azacyclics for treating cns disorders |
| DE3789039T2 (de) * | 1986-06-27 | 1994-06-09 | Beecham Group Plc | Verbrückte bicyclische N-heterocyclische Verbindungen. |
| NZ227841A (en) * | 1988-02-12 | 1991-08-27 | Merck Sharp & Dohme | Heterocyclic compounds with at least two non-condensed five membered rings and pharmaceutical compositions |
| JP3353406B2 (ja) * | 1993-08-16 | 2002-12-03 | 富士電機株式会社 | 燃料電池発電装置 |
-
1988
- 1988-08-31 NZ NZ225999A patent/NZ225999A/en unknown
- 1988-09-01 IL IL8764388A patent/IL87643A/en not_active IP Right Cessation
- 1988-09-01 AT AT88308127T patent/ATE111464T1/de not_active IP Right Cessation
- 1988-09-01 DE DE3851498T patent/DE3851498T2/de not_active Revoked
- 1988-09-01 EP EP88308127A patent/EP0307142B1/de not_active Revoked
- 1988-09-05 PT PT88422A patent/PT88422B/pt not_active IP Right Cessation
- 1988-09-09 DK DK503188A patent/DK503188A/da not_active Application Discontinuation
- 1988-09-09 AU AU22073/88A patent/AU626209B2/en not_active Ceased
- 1988-09-10 KR KR1019880011706A patent/KR890005103A/ko not_active Ceased
- 1988-09-10 JP JP63225567A patent/JPH01104070A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP0307142A1 (de) | 1989-03-15 |
| EP0307142B1 (de) | 1994-09-14 |
| DE3851498D1 (de) | 1994-10-20 |
| DE3851498T2 (de) | 1995-05-04 |
| AU2207388A (en) | 1989-03-16 |
| DK503188A (da) | 1989-05-01 |
| ATE111464T1 (de) | 1994-09-15 |
| JPH01104070A (ja) | 1989-04-21 |
| AU626209B2 (en) | 1992-07-23 |
| PT88422B (pt) | 1992-10-30 |
| IL87643A0 (en) | 1989-02-28 |
| KR890005103A (ko) | 1989-05-11 |
| NZ225999A (en) | 1992-04-28 |
| DK503188D0 (da) | 1988-09-09 |
| PT88422A (pt) | 1989-07-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM9K | Patent not in force due to non-payment of renewal fees |