EA002352B1 - Производные индазоламида в качестве серотонинергических агентов - Google Patents
Производные индазоламида в качестве серотонинергических агентов Download PDFInfo
- Publication number
- EA002352B1 EA002352B1 EA199900935A EA199900935A EA002352B1 EA 002352 B1 EA002352 B1 EA 002352B1 EA 199900935 A EA199900935 A EA 199900935A EA 199900935 A EA199900935 A EA 199900935A EA 002352 B1 EA002352 B1 EA 002352B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- compound
- formula
- pharmaceutically acceptable
- alkyl
- group
- Prior art date
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- DITBWPUMEUDVLU-UHFFFAOYSA-N 1h-indazole-3-carboxamide Chemical class C1=CC=C2C(C(=O)N)=NNC2=C1 DITBWPUMEUDVLU-UHFFFAOYSA-N 0.000 title claims description 4
- 239000000952 serotonin receptor agonist Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 71
- -1 aminosulphonylmethyl Chemical group 0.000 claims abstract description 36
- 150000003839 salts Chemical class 0.000 claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000002253 acid Chemical group 0.000 claims abstract description 13
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 13
- 150000007524 organic acids Chemical class 0.000 claims abstract description 13
- 239000003085 diluting agent Substances 0.000 claims abstract description 12
- 239000000203 mixture Substances 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 8
- 125000003118 aryl group Chemical group 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 6
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims abstract description 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 5
- 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 abstract description 5
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims abstract description 5
- 150000002367 halogens Chemical group 0.000 claims abstract description 5
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
- LTEKQAPRXFBRNN-UHFFFAOYSA-N piperidin-4-ylmethanamine Chemical compound NCC1CCNCC1 LTEKQAPRXFBRNN-UHFFFAOYSA-N 0.000 claims abstract description 4
- 230000002152 alkylating effect Effects 0.000 claims abstract description 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims abstract description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 3
- 125000003838 furazanyl group Chemical group 0.000 claims abstract description 3
- 125000002541 furyl group Chemical group 0.000 claims abstract description 3
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims abstract description 3
- 125000002636 imidazolinyl group Chemical group 0.000 claims abstract description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims abstract description 3
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims abstract description 3
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims abstract description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims abstract description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 3
- 125000002098 pyridazinyl group Chemical group 0.000 claims abstract description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 3
- 125000001422 pyrrolinyl group Chemical group 0.000 claims abstract description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 3
- 229910052801 chlorine Inorganic materials 0.000 claims abstract 4
- 239000000460 chlorine Substances 0.000 claims abstract 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract 2
- 229910052794 bromium Chemical group 0.000 claims abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 230000010933 acylation Effects 0.000 claims description 2
- 238000005917 acylation reaction Methods 0.000 claims description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 125000002755 pyrazolinyl group Chemical group 0.000 abstract description 5
- 238000006243 chemical reaction Methods 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 150000007513 acids Chemical class 0.000 abstract 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 abstract 1
- 125000004193 piperazinyl group Chemical group 0.000 abstract 1
- 125000003386 piperidinyl group Chemical group 0.000 abstract 1
- 125000003831 tetrazolyl group Chemical group 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 37
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000000921 elemental analysis Methods 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 230000003042 antagnostic effect Effects 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- LLHKTXMUSWEWPI-UHFFFAOYSA-N 1-propan-2-ylindazole-3-carbonyl chloride Chemical compound C1=CC=C2N(C(C)C)N=C(C(Cl)=O)C2=C1 LLHKTXMUSWEWPI-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 206010003658 Atrial Fibrillation Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 206010046543 Urinary incontinence Diseases 0.000 description 2
- 230000001270 agonistic effect Effects 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000008991 intestinal motility Effects 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- ILMRKUITBNLROD-PAMPIZDHSA-N (z)-but-2-enedioic acid;hydrate Chemical compound O.OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O ILMRKUITBNLROD-PAMPIZDHSA-N 0.000 description 1
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
- PRYNGBWWKDSBAP-UHFFFAOYSA-N 1-propan-2-yl-n-[[1-(2-pyridin-2-ylethyl)piperidin-4-yl]methyl]indazole-3-carboxamide;hydrochloride Chemical compound Cl.C12=CC=CC=C2N(C(C)C)N=C1C(=O)NCC(CC1)CCN1CCC1=CC=CC=N1 PRYNGBWWKDSBAP-UHFFFAOYSA-N 0.000 description 1
- FHUPHXAYPNYFIU-UHFFFAOYSA-N 1-propan-2-ylindazole-3-carboxylic acid Chemical compound C1=CC=C2N(C(C)C)N=C(C(O)=O)C2=C1 FHUPHXAYPNYFIU-UHFFFAOYSA-N 0.000 description 1
- CLVNTYZKUHNUEF-UHFFFAOYSA-N 2-(2-chloroethyl)-1-methylpyrrolidine Chemical compound CN1CCCC1CCCl CLVNTYZKUHNUEF-UHFFFAOYSA-N 0.000 description 1
- JRQAAYVLPPGEHT-UHFFFAOYSA-N 2-bromoethylcyclohexane Chemical compound BrCCC1CCCCC1 JRQAAYVLPPGEHT-UHFFFAOYSA-N 0.000 description 1
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
- QJENXUJKEIZMGC-UHFFFAOYSA-N 2-methylpropyl 1-propan-2-ylindazole-3-carboxylate Chemical compound C1=CC=C2C(C(=O)OCC(C)C)=NN(C(C)C)C2=C1 QJENXUJKEIZMGC-UHFFFAOYSA-N 0.000 description 1
- SDGKBHBQHDAYMI-UHFFFAOYSA-N 2-methylpropyl 1h-indazole-3-carboxylate Chemical compound C1=CC=C2C(C(=O)OCC(C)C)=NNC2=C1 SDGKBHBQHDAYMI-UHFFFAOYSA-N 0.000 description 1
- PRXXDNPQVBXHQV-UHFFFAOYSA-N 2-methylpropyl 2-propan-2-ylindazole-3-carboxylate Chemical compound C1=CC=CC2=C(C(=O)OCC(C)C)N(C(C)C)N=C21 PRXXDNPQVBXHQV-UHFFFAOYSA-N 0.000 description 1
- KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical compound C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-UHFFFAOYSA-N 0.000 description 1
- DYYVTFCYVZEQDG-UHFFFAOYSA-N 4-(2-bromoethyl)phenol Chemical compound OC1=CC=C(CCBr)C=C1 DYYVTFCYVZEQDG-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
- XPBQQAHIVODAIC-UHFFFAOYSA-N 4-bromobutylbenzene Chemical compound BrCCCCC1=CC=CC=C1 XPBQQAHIVODAIC-UHFFFAOYSA-N 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940082988 antihypertensives serotonin antagonists Drugs 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 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
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 125000005909 ethyl alcohol group Chemical group 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000005176 gastrointestinal motility Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- DDMSOGRHSPMSLW-UHFFFAOYSA-N indazole-1-carboxamide Chemical compound C1=CC=C2N(C(=O)N)N=CC2=C1 DDMSOGRHSPMSLW-UHFFFAOYSA-N 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000008855 peristalsis Effects 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 102220072554 rs372717179 Human genes 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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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- 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
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- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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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
- A61P25/22—Anxiolytics
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- 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
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- 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)
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- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
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- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Paints Or Removers (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT97MI000867A IT1291569B1 (it) | 1997-04-15 | 1997-04-15 | Indazolammidi come agenti serotoninergici |
| PCT/EP1998/002129 WO1998046589A2 (en) | 1997-04-15 | 1998-04-02 | Indazole amide compounds as serotoninergic agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA199900935A1 EA199900935A1 (ru) | 2000-04-24 |
| EA002352B1 true EA002352B1 (ru) | 2002-04-25 |
Family
ID=11376888
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA199900935A EA002352B1 (ru) | 1997-04-15 | 1998-04-02 | Производные индазоламида в качестве серотонинергических агентов |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US6197769B1 (https=) |
| EP (1) | EP0975623B1 (https=) |
| JP (2) | JP4578581B2 (https=) |
| KR (1) | KR100563867B1 (https=) |
| CN (1) | CN1318416C (https=) |
| AR (1) | AR012426A1 (https=) |
| AT (1) | ATE219490T1 (https=) |
| AU (1) | AU740360B2 (https=) |
| BG (1) | BG64006B1 (https=) |
| CA (1) | CA2286870C (https=) |
| CZ (1) | CZ295190B6 (https=) |
| DE (1) | DE69806141T2 (https=) |
| DK (1) | DK0975623T3 (https=) |
| EA (1) | EA002352B1 (https=) |
| ES (1) | ES2178205T3 (https=) |
| GE (1) | GEP20022654B (https=) |
| HU (1) | HU227973B1 (https=) |
| IL (1) | IL132127A (https=) |
| IT (1) | IT1291569B1 (https=) |
| PL (1) | PL193308B1 (https=) |
| PT (1) | PT975623E (https=) |
| SK (1) | SK284731B6 (https=) |
| TR (1) | TR199902546T2 (https=) |
| UA (1) | UA58550C2 (https=) |
| WO (1) | WO1998046589A2 (https=) |
| ZA (1) | ZA982926B (https=) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1291569B1 (it) * | 1997-04-15 | 1999-01-11 | Angelini Ricerche Spa | Indazolammidi come agenti serotoninergici |
| PL364625A1 (en) | 2001-02-23 | 2004-12-13 | Merck & Co, Inc. | N-substituted nonaryl-heterocyclic nmda/nr2b antagonists |
| WO2002080928A1 (en) | 2001-04-03 | 2002-10-17 | Merck & Co., Inc. | N-substituted nonaryl-heterocyclo amidyl nmda/nr2b antagonists |
| ITMI20030287A1 (it) | 2003-02-18 | 2004-08-19 | Acraf | Indazolammidi dotate di attivita' analgesica metodo, per |
| ITMI20030972A1 (it) * | 2003-05-15 | 2004-11-16 | Acraf | Indazolo dotato di attivita' analgesica, metodo per prepararlo e composizione farmaceutica che lo comprende. |
| ITMI20031468A1 (it) * | 2003-07-18 | 2005-01-19 | Acraf | Farmaco ativo nel dolore neuropatico |
| TW200533348A (en) * | 2004-02-18 | 2005-10-16 | Theravance Inc | Indazole-carboxamide compounds as 5-ht4 receptor agonists |
| TWI351282B (en) | 2004-04-07 | 2011-11-01 | Theravance Inc | Quinolinone-carboxamide compounds as 5-ht4 recepto |
| US7728006B2 (en) * | 2004-04-07 | 2010-06-01 | Theravance, Inc. | Quinolinone-carboxamide compounds as 5-HT4 receptor agonists |
| US8309575B2 (en) | 2004-04-07 | 2012-11-13 | Theravance, Inc. | Quinolinone-carboxamide compounds as 5-HT4 receptor agonists |
| US7399862B2 (en) * | 2004-11-05 | 2008-07-15 | Theravance, Inc. | 5-HT4 receptor agonist compounds |
| WO2006052889A2 (en) * | 2004-11-05 | 2006-05-18 | Theravance, Inc. | Quinolinone-carboxamide compounds |
| CA2588037A1 (en) * | 2004-12-22 | 2006-06-29 | Theravance, Inc. | Indazole-carboxamide compounds |
| WO2006088988A1 (en) * | 2005-02-17 | 2006-08-24 | Theravance, Inc. | Crystalline form of an indazole-carboxamide compound |
| CN101163701A (zh) * | 2005-03-02 | 2008-04-16 | 施万制药 | 作为5-ht4受体激动剂的喹啉酮化合物 |
| ITMI20062230A1 (it) * | 2006-11-22 | 2008-05-23 | Acraf | Composto 2-alchil-indazolico procedimento per preparalo e composizione farmaceutica che lo comprende |
| UA99927C2 (uk) * | 2007-11-12 | 2012-10-25 | Ацьенде Кимике Риуните Анджелини Франческо А.Чи.Р.А.Ф. С.П.А. | Медикамент, який є активним при невропатичному болі |
| US8377968B2 (en) | 2008-06-02 | 2013-02-19 | Zalicus Pharmaceuticals, Ltd. | N-piperidinyl acetamide derivatives as calcium channel blockers |
| KR20140041519A (ko) * | 2011-06-07 | 2014-04-04 | 다이닛본 스미토모 세이야꾸 가부시끼가이샤 | 인다졸-유도체 및 피롤로피리딘-유도체 및 그의 약제학적 용도 |
| CA2860250C (en) * | 2012-02-21 | 2020-11-10 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | 1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors |
| RS54539B1 (sr) * | 2012-02-21 | 2016-06-30 | Aziende Chimiche Riunite Angelini Francesco - A.C.R.A.F. - S.P.A. | Upotreba 1h-indazol-3-karboksamidnih jedinjenja kao inhibitora kinaze 3-beta glikogen sintetaze |
| EP2961403A4 (en) | 2013-03-01 | 2016-11-30 | Zalicus Pharmaceuticals Ltd | HETEROCYCLIC INHIBITORS OF SODIUM CHANNEL |
| CN114340670B (zh) | 2019-07-11 | 2026-02-17 | 普拉克西斯精密药物股份有限公司 | T-型钙通道调节剂的制剂及其使用方法 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0501322A1 (en) * | 1991-02-25 | 1992-09-02 | Glaxo Group Limited | 3-Piperidinylmethylcarboxylate substituted indoles |
| WO1993003725A1 (en) * | 1991-08-20 | 1993-03-04 | Smithkline Beecham Plc | 5-ht4 receptor antagonists |
| EP0732333A1 (en) * | 1995-03-16 | 1996-09-18 | Eli Lilly And Company | Indazolecarboxamides |
| WO1996038420A1 (en) * | 1995-05-31 | 1996-12-05 | Nisshin Flour Milling Co., Ltd. | Indazole derivatives having monocyclic amino group |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1291569B1 (it) * | 1997-04-15 | 1999-01-11 | Angelini Ricerche Spa | Indazolammidi come agenti serotoninergici |
-
1997
- 1997-04-15 IT IT97MI000867A patent/IT1291569B1/it active IP Right Grant
-
1998
- 1998-02-04 UA UA99116211A patent/UA58550C2/uk unknown
- 1998-04-02 EA EA199900935A patent/EA002352B1/ru not_active IP Right Cessation
- 1998-04-02 DK DK98919257T patent/DK0975623T3/da active
- 1998-04-02 DE DE69806141T patent/DE69806141T2/de not_active Expired - Lifetime
- 1998-04-02 ES ES98919257T patent/ES2178205T3/es not_active Expired - Lifetime
- 1998-04-02 JP JP54347598A patent/JP4578581B2/ja not_active Expired - Fee Related
- 1998-04-02 CN CNB988041987A patent/CN1318416C/zh not_active Expired - Fee Related
- 1998-04-02 PT PT98919257T patent/PT975623E/pt unknown
- 1998-04-02 CZ CZ19993625A patent/CZ295190B6/cs not_active IP Right Cessation
- 1998-04-02 AT AT98919257T patent/ATE219490T1/de active
- 1998-04-02 CA CA002286870A patent/CA2286870C/en not_active Expired - Fee Related
- 1998-04-02 IL IL13212798A patent/IL132127A/xx not_active IP Right Cessation
- 1998-04-02 WO PCT/EP1998/002129 patent/WO1998046589A2/en not_active Ceased
- 1998-04-02 HU HU0002057A patent/HU227973B1/hu not_active IP Right Cessation
- 1998-04-02 PL PL336348A patent/PL193308B1/pl unknown
- 1998-04-02 KR KR1019997009198A patent/KR100563867B1/ko not_active Expired - Fee Related
- 1998-04-02 GE GEAP19985083A patent/GEP20022654B/en unknown
- 1998-04-02 AU AU72159/98A patent/AU740360B2/en not_active Ceased
- 1998-04-02 SK SK1423-99A patent/SK284731B6/sk not_active IP Right Cessation
- 1998-04-02 EP EP98919257A patent/EP0975623B1/en not_active Expired - Lifetime
- 1998-04-02 US US09/403,007 patent/US6197769B1/en not_active Expired - Lifetime
- 1998-04-02 TR TR1999/02546T patent/TR199902546T2/xx unknown
- 1998-04-06 ZA ZA982926A patent/ZA982926B/xx unknown
- 1998-04-15 AR ARP980101721A patent/AR012426A1/es active IP Right Grant
-
1999
- 1999-11-05 BG BG103863A patent/BG64006B1/bg unknown
-
2010
- 2010-04-26 JP JP2010100701A patent/JP5237324B2/ja not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0501322A1 (en) * | 1991-02-25 | 1992-09-02 | Glaxo Group Limited | 3-Piperidinylmethylcarboxylate substituted indoles |
| WO1993003725A1 (en) * | 1991-08-20 | 1993-03-04 | Smithkline Beecham Plc | 5-ht4 receptor antagonists |
| EP0732333A1 (en) * | 1995-03-16 | 1996-09-18 | Eli Lilly And Company | Indazolecarboxamides |
| WO1996038420A1 (en) * | 1995-05-31 | 1996-12-05 | Nisshin Flour Milling Co., Ltd. | Indazole derivatives having monocyclic amino group |
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG MD TJ TM RU |