AU740360B2 - Indazole amide compounds as serotoninergic agents - Google Patents
Indazole amide compounds as serotoninergic agents Download PDFInfo
- Publication number
- AU740360B2 AU740360B2 AU72159/98A AU7215998A AU740360B2 AU 740360 B2 AU740360 B2 AU 740360B2 AU 72159/98 A AU72159/98 A AU 72159/98A AU 7215998 A AU7215998 A AU 7215998A AU 740360 B2 AU740360 B2 AU 740360B2
- Authority
- AU
- Australia
- Prior art keywords
- compound
- formula
- pharmaceutically acceptable
- group
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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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 description 2
- 239000000952 serotonin receptor agonist Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 56
- -1 aminosulphonylmethyl Chemical group 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 15
- 239000002253 acid Chemical group 0.000 claims description 10
- 239000003085 diluting agent Substances 0.000 claims description 9
- 150000007522 mineralic acids Chemical class 0.000 claims description 9
- 150000007524 organic acids Chemical class 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical group 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- LTEKQAPRXFBRNN-UHFFFAOYSA-N piperidin-4-ylmethanamine Chemical compound NCC1CCNCC1 LTEKQAPRXFBRNN-UHFFFAOYSA-N 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- 230000002152 alkylating effect Effects 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Chemical group 0.000 claims description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000003838 furazanyl group Chemical group 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 2
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical group IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 2
- 125000002755 pyrazolinyl group Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000004306 triazinyl group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
- 238000000921 elemental analysis Methods 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- 239000002552 dosage form Substances 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 241000894007 species Species 0.000 description 4
- IHZRQQYHYALFRG-UHFFFAOYSA-N 1-propan-2-ylindazole-3-carboxamide Chemical compound C1=CC=C2N(C(C)C)N=C(C(N)=O)C2=C1 IHZRQQYHYALFRG-UHFFFAOYSA-N 0.000 description 3
- 108091005482 5-HT4 receptors Proteins 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- NRYMXWPDCLAULN-UHFFFAOYSA-N Cl.CC(C)N1N=C(C2=CC=CC=C12)C(=O)N Chemical compound Cl.CC(C)N1N=C(C2=CC=CC=C12)C(=O)N NRYMXWPDCLAULN-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 230000003042 antagnostic effect Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 229940076279 serotonin Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 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 2
- 238000005160 1H NMR spectroscopy Methods 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
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-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
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 206010003119 arrhythmia Diseases 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
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000008991 intestinal motility Effects 0.000 description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
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- 238000012360 testing method Methods 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- KNUKUWNSGVICSX-UHFFFAOYSA-N (1-benzylpiperidin-4-yl)methanamine Chemical compound C1CC(CN)CCN1CC1=CC=CC=C1 KNUKUWNSGVICSX-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-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
- 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
- KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical compound C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-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
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 101000585693 Homo sapiens Mitochondrial 2-oxodicarboxylate carrier Proteins 0.000 description 1
- 101001041245 Homo sapiens Ornithine decarboxylase Proteins 0.000 description 1
- 102100021079 Ornithine decarboxylase Human genes 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- KBHCQTYLQFEISG-UHFFFAOYSA-N S(=O)(Cl)Cl.C(C)(C)N1N=C(C2=CC=CC=C12)C(=O)Cl Chemical compound S(=O)(Cl)Cl.C(C)(C)N1N=C(C2=CC=CC=C12)C(=O)Cl KBHCQTYLQFEISG-UHFFFAOYSA-N 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
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- 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
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- 238000004090 dissolution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000005216 enteric neuron Anatomy 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 125000005909 ethyl alcohol group Chemical group 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
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- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
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- 229910052739 hydrogen Inorganic materials 0.000 description 1
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- 239000000543 intermediate Substances 0.000 description 1
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- CRKKBLJOBGERJR-UHFFFAOYSA-N n-(piperidin-4-ylmethyl)-1-propan-2-ylindazole-3-carboxamide Chemical compound C12=CC=CC=C2N(C(C)C)N=C1C(=O)NCC1CCNCC1 CRKKBLJOBGERJR-UHFFFAOYSA-N 0.000 description 1
- FZKNVYOUIUTVNM-UHFFFAOYSA-N n-(piperidin-4-ylmethyl)-1-propan-2-ylindazole-3-carboxamide;hydrochloride Chemical compound Cl.C12=CC=CC=C2N(C(C)C)N=C1C(=O)NCC1CCNCC1 FZKNVYOUIUTVNM-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
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- 229910052763 palladium Inorganic materials 0.000 description 1
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- 239000002831 pharmacologic agent Substances 0.000 description 1
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- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
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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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
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- A61P13/10—Drugs for disorders of the urinary system of the bladder
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- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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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
- A61P9/06—Antiarrhythmics
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- 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 (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI97A000867 | 1997-04-15 | ||
| 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 |
|---|---|
| AU7215998A AU7215998A (en) | 1998-11-11 |
| AU740360B2 true AU740360B2 (en) | 2001-11-01 |
Family
ID=11376888
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU72159/98A Ceased AU740360B2 (en) | 1997-04-15 | 1998-04-02 | Indazole amide compounds as serotoninergic agents |
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 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9103862D0 (en) * | 1991-02-25 | 1991-04-10 | Glaxo Group Ltd | Chemical compounds |
| CA2116024A1 (en) * | 1991-08-20 | 1993-03-04 | Francis David King | 5-ht4 receptor antagonists |
| IL117438A (en) * | 1995-03-16 | 2001-12-23 | Lilly Co Eli | Indazolecarboxamides, their preparation and pharmaceutical compositions containing them |
| EP0829474B1 (en) * | 1995-05-31 | 2003-04-09 | Nisshin Seifun Group Inc. | Indazole derivatives having monocyclic amino group |
| 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
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