JP2007523175A - ５−ｈｔ４レセプターアゴニストとしてのインダゾール−カルボキシアミド化合物 - Google Patents
５−ｈｔ４レセプターアゴニストとしてのインダゾール−カルボキシアミド化合物 Download PDFInfo
- Publication number
- JP2007523175A JP2007523175A JP2006554207A JP2006554207A JP2007523175A JP 2007523175 A JP2007523175 A JP 2007523175A JP 2006554207 A JP2006554207 A JP 2006554207A JP 2006554207 A JP2006554207 A JP 2006554207A JP 2007523175 A JP2007523175 A JP 2007523175A
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- JP
- Japan
- Prior art keywords
- indazole
- carboxylic acid
- azabicyclo
- ethyl
- amide
- 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.)
- Pending
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- 239000000018 receptor agonist Substances 0.000 title abstract description 17
- 229940044601 receptor agonist Drugs 0.000 title abstract description 17
- DITBWPUMEUDVLU-UHFFFAOYSA-N 1h-indazole-3-carboxamide Chemical class C1=CC=C2C(C(=O)N)=NNC2=C1 DITBWPUMEUDVLU-UHFFFAOYSA-N 0.000 title description 4
- 108091005482 5-HT4 receptors Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 225
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims abstract description 140
- 238000000034 method Methods 0.000 claims abstract description 81
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- 102000005962 receptors Human genes 0.000 claims abstract description 50
- 108020003175 receptors Proteins 0.000 claims abstract description 50
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 39
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- 230000000694 effects Effects 0.000 claims abstract description 30
- 230000008569 process Effects 0.000 claims abstract description 19
- 239000012453 solvate Substances 0.000 claims abstract description 17
- 201000010099 disease Diseases 0.000 claims abstract description 16
- -1 4-acetylpiperazin-1-yl Chemical group 0.000 claims description 138
- 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 claims description 127
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 99
- 125000000217 alkyl group Chemical group 0.000 claims description 52
- 150000001408 amides Chemical class 0.000 claims description 41
- 239000008194 pharmaceutical composition Substances 0.000 claims description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 23
- 241000124008 Mammalia Species 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
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- 239000012472 biological sample Substances 0.000 claims description 10
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 10
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- IEIAQSWMJMZELU-UHFFFAOYSA-N 5-fluoro-1-propan-2-ylindazole-3-carboxylic acid Chemical compound FC1=CC=C2N(C(C)C)N=C(C(O)=O)C2=C1 IEIAQSWMJMZELU-UHFFFAOYSA-N 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 7
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims description 7
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- 238000005859 coupling reaction Methods 0.000 claims description 5
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- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 208000007542 Paresis Diseases 0.000 claims description 4
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- SRLYWTDJCHALPO-UHFFFAOYSA-N 1-propylindazole-3-carboxylic acid Chemical compound C1=CC=C2N(CCC)N=C(C(O)=O)C2=C1 SRLYWTDJCHALPO-UHFFFAOYSA-N 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- MENILFUADYEXNU-UHFFFAOYSA-N tert-butyl 3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1C(=O)CC2CCC1N2C(=O)OC(C)(C)C MENILFUADYEXNU-UHFFFAOYSA-N 0.000 claims description 3
- 229910052723 transition metal Inorganic materials 0.000 claims description 3
- 150000003624 transition metals Chemical class 0.000 claims description 3
- HIOJBUUZILLMSD-UHFFFAOYSA-N 1-butylindazole-3-carboxylic acid Chemical compound C1=CC=C2N(CCCC)N=C(C(O)=O)C2=C1 HIOJBUUZILLMSD-UHFFFAOYSA-N 0.000 claims description 2
- OVTXQAXXRCDBCP-UHFFFAOYSA-N 1-cyclobutylindazole-3-carboxylic acid Chemical compound C12=CC=CC=C2C(C(=O)O)=NN1C1CCC1 OVTXQAXXRCDBCP-UHFFFAOYSA-N 0.000 claims description 2
- YOZGRUDRUTYFDN-UHFFFAOYSA-N 1-cyclopentylindazole-3-carboxylic acid Chemical compound C12=CC=CC=C2C(C(=O)O)=NN1C1CCCC1 YOZGRUDRUTYFDN-UHFFFAOYSA-N 0.000 claims description 2
- 230000006870 function Effects 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 4
- 230000001568 sexual effect Effects 0.000 claims 1
- NZJKEPNCNBWESN-UHFFFAOYSA-N tert-butyl 3-amino-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1C(N)CC2CCC1N2C(=O)OC(C)(C)C NZJKEPNCNBWESN-UHFFFAOYSA-N 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 56
- 238000002360 preparation method Methods 0.000 abstract description 32
- DDMSOGRHSPMSLW-UHFFFAOYSA-N indazole-1-carboxamide Chemical compound C1=CC=C2N(C(=O)N)N=CC2=C1 DDMSOGRHSPMSLW-UHFFFAOYSA-N 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 74
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- 238000003786 synthesis reaction Methods 0.000 description 18
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- 239000012528 membrane Substances 0.000 description 15
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
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- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- CTJYSVRXJDACIO-UHFFFAOYSA-N tert-butyl thiomorpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCSCC1 CTJYSVRXJDACIO-UHFFFAOYSA-N 0.000 description 1
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- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 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
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000005591 trimellitate group Chemical group 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
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- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
-
- 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
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
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- G—PHYSICS
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- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70571—Assays involving receptors, cell surface antigens or cell surface determinants for neuromediators, e.g. serotonin receptor, dopamine receptor
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- Endocrinology (AREA)
- Obesity (AREA)
- Nutrition Science (AREA)
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- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
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| PCT/US2005/005070 WO2005080389A1 (en) | 2004-02-18 | 2005-02-17 | Indazole-carboxamide compounds as 5-ht4 receptor agonists |
Publications (2)
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| JP2007523175A true JP2007523175A (ja) | 2007-08-16 |
| JP2007523175A5 JP2007523175A5 (https=) | 2008-03-13 |
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| JP (1) | JP2007523175A (https=) |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2012169649A1 (en) * | 2011-06-07 | 2012-12-13 | Dainippon Sumitomo Pharma Co., Ltd. | Indazole- and pyrrolopyridine-derivative and pharmaceutical use thereof |
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| US8309575B2 (en) | 2004-04-07 | 2012-11-13 | Theravance, Inc. | Quinolinone-carboxamide compounds as 5-HT4 receptor agonists |
| US7728006B2 (en) * | 2004-04-07 | 2010-06-01 | Theravance, Inc. | Quinolinone-carboxamide compounds as 5-HT4 receptor agonists |
| TWI351282B (en) | 2004-04-07 | 2011-11-01 | Theravance Inc | Quinolinone-carboxamide compounds as 5-ht4 recepto |
| 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 |
| EP1902053B1 (en) * | 2005-06-07 | 2011-01-12 | Theravance, Inc. | Benzoimidazolone-carboxamide compounds as 5-ht4 receptor agonists |
| US20080262040A1 (en) * | 2005-10-25 | 2008-10-23 | Smithkline Beecham Corporation | Chemical Compounds |
| MY143574A (en) * | 2005-11-22 | 2011-05-31 | Theravance Inc | Carbamate compounds as 5-ht4 receptor agonists |
| GB0525068D0 (en) | 2005-12-08 | 2006-01-18 | Novartis Ag | Organic compounds |
| CN101384588B (zh) * | 2006-02-16 | 2011-08-31 | 施万制药 | 制备5-ht4受体激动剂化合物的中间体的方法 |
| KR100812499B1 (ko) * | 2006-10-16 | 2008-03-11 | 이도훈 | 항경련제 |
| WO2008101728A1 (de) * | 2007-02-23 | 2008-08-28 | K.H.S. Pharma Holding Gmbh | Verfahren zur herstellung von azoniaspironortropinestern und von nortropan-3-on verbindungen |
| EP2241567A4 (en) * | 2008-02-13 | 2011-11-09 | Eisai R&D Man Co Ltd | Bicycloamine DERIVATIVE |
| US8349852B2 (en) | 2009-01-13 | 2013-01-08 | Novartis Ag | Quinazolinone derivatives useful as vanilloid antagonists |
| AR080056A1 (es) | 2010-02-01 | 2012-03-07 | Novartis Ag | Derivados de ciclohexil-amida como antagonistas de los receptores de crf |
| WO2011092290A1 (en) | 2010-02-01 | 2011-08-04 | Novartis Ag | Pyrazolo[5,1b]oxazole derivatives as crf-1 receptor antagonists |
| EP2531490B1 (en) | 2010-02-02 | 2014-10-15 | Novartis AG | Cyclohexyl amide derivatives as crf receptor antagonists |
| JP6023926B2 (ja) * | 2010-02-12 | 2016-11-09 | 株式会社ＡｓｋＡｔ | 認知症治療のための５−ｈｔ４受容体アゴニスト |
| AR086554A1 (es) | 2011-05-27 | 2014-01-08 | Novartis Ag | Derivados de la piperidina 3-espirociclica como agonistas de receptores de la ghrelina |
| JP2015525202A (ja) | 2012-05-03 | 2015-09-03 | ノバルティス アーゲー | グレリン受容体アゴニストとしての２，７−ジアザ−スピロ［４，５］デカ−７−イル誘導体のｌ−リンゴ酸塩およびその結晶形態 |
| JP2014133739A (ja) * | 2012-12-12 | 2014-07-24 | Dainippon Sumitomo Pharma Co Ltd | インダゾール誘導体またはピロロピリジン誘導体からなる医薬 |
| RS60804B1 (sr) * | 2014-08-16 | 2020-10-30 | Suven Life Sciences Ltd | Proces proizvodnje 1-izopropil-3-{5-[1-(3-metoksipropil)piperidin-4-il]-[1,3,4]oksadiazol-2-il}-1h-indazol oksalata u velikom obimu |
| CN112805282A (zh) * | 2019-09-12 | 2021-05-14 | 广东东阳光药业有限公司 | 吲唑-甲酰胺衍生物及其用途 |
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2005
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2006
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2010
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012169649A1 (en) * | 2011-06-07 | 2012-12-13 | Dainippon Sumitomo Pharma Co., Ltd. | Indazole- and pyrrolopyridine-derivative and pharmaceutical use thereof |
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| NO20064156L (no) | 2006-11-10 |
| CA2553696A1 (en) | 2005-09-01 |
| TW200533348A (en) | 2005-10-16 |
| US20050197335A1 (en) | 2005-09-08 |
| CN1922175A (zh) | 2007-02-28 |
| WO2005080389A1 (en) | 2005-09-01 |
| IL177059A0 (en) | 2006-12-10 |
| US20080146807A1 (en) | 2008-06-19 |
| US20100261716A1 (en) | 2010-10-14 |
| AU2005214368A1 (en) | 2005-09-01 |
| AR047681A1 (es) | 2006-02-01 |
| EP1718643A1 (en) | 2006-11-08 |
| BRPI0507791A (pt) | 2007-07-17 |
| MA28435B1 (fr) | 2007-02-01 |
| ZA200606479B (en) | 2008-01-30 |
| US7351704B2 (en) | 2008-04-01 |
| US8044045B2 (en) | 2011-10-25 |
| US7674908B2 (en) | 2010-03-09 |
| RU2006133320A (ru) | 2008-03-27 |
| KR20060132727A (ko) | 2006-12-21 |
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