EA011714B1 - Производные n-(1h-индолил)-1h-индол-2-карбоксамидов, их получение и их применение в терапии - Google Patents
Производные n-(1h-индолил)-1h-индол-2-карбоксамидов, их получение и их применение в терапии Download PDFInfo
- Publication number
- EA011714B1 EA011714B1 EA200700400A EA200700400A EA011714B1 EA 011714 B1 EA011714 B1 EA 011714B1 EA 200700400 A EA200700400 A EA 200700400A EA 200700400 A EA200700400 A EA 200700400A EA 011714 B1 EA011714 B1 EA 011714B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- indole
- methyl
- indol
- carboxamide
- alkyl
- Prior art date
Links
- 230000001225 therapeutic effect Effects 0.000 title abstract description 3
- 238000002360 preparation method Methods 0.000 title description 6
- NMOYGMDGSQDQRX-UHFFFAOYSA-N n-indol-1-yl-1h-indole-2-carboxamide Chemical class C1=CC=C2NC(C(NN3C4=CC=CC=C4C=C3)=O)=CC2=C1 NMOYGMDGSQDQRX-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 103
- -1 7-indolyl group Chemical group 0.000 claims abstract description 91
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 31
- 125000003118 aryl group Chemical group 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 125000005843 halogen group Chemical group 0.000 claims abstract description 16
- 239000012453 solvate Substances 0.000 claims abstract description 15
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000002253 acid Substances 0.000 claims abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 9
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims abstract description 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims abstract description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical group C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims abstract description 4
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 4
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 17
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- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 14
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- 230000002265 prevention Effects 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 8
- IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical class C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 claims description 7
- 210000001508 eye Anatomy 0.000 claims description 7
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
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- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
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- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims description 4
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- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- LPYLDTGFZCMNEE-UHFFFAOYSA-N n-(1-methylindol-5-yl)-1-(4-propan-2-ylphenyl)indole-2-carboxamide Chemical compound C1=CC(C(C)C)=CC=C1N1C2=CC=CC=C2C=C1C(=O)NC1=CC=C(N(C)C=C2)C2=C1 LPYLDTGFZCMNEE-UHFFFAOYSA-N 0.000 claims description 3
- USMBQPADXNCRMG-UHFFFAOYSA-N n-(1-methylindol-5-yl)-1-[3-(trifluoromethyl)phenyl]indole-2-carboxamide Chemical compound C=1C=C2N(C)C=CC2=CC=1NC(=O)C1=CC2=CC=CC=C2N1C1=CC=CC(C(F)(F)F)=C1 USMBQPADXNCRMG-UHFFFAOYSA-N 0.000 claims description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
- WZJFMHIURRCYNA-UHFFFAOYSA-N 5-fluoro-1-[(3-fluorophenyl)methyl]-n-(1-methylindol-5-yl)indole-2-carboxamide Chemical compound C=1C=C2N(C)C=CC2=CC=1NC(=O)C1=CC2=CC(F)=CC=C2N1CC1=CC=CC(F)=C1 WZJFMHIURRCYNA-UHFFFAOYSA-N 0.000 claims description 2
- XTJFHWOUXRBLLJ-UHFFFAOYSA-N 5-methoxy-n-(1-methylindol-5-yl)-1-[[3-(trifluoromethyl)phenyl]methyl]indole-2-carboxamide Chemical compound C=1C=C2N(C)C=CC2=CC=1NC(=O)C1=CC2=CC(OC)=CC=C2N1CC1=CC=CC(C(F)(F)F)=C1 XTJFHWOUXRBLLJ-UHFFFAOYSA-N 0.000 claims description 2
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- 230000003217 anti-cancerogenic effect Effects 0.000 claims description 2
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- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
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- MEWNQVJSCZZUMB-UHFFFAOYSA-N n-(1-methylindol-5-yl)-1-(3-propan-2-ylphenyl)-5-(trifluoromethoxy)indole-2-carboxamide Chemical compound CC(C)C1=CC=CC(N2C3=CC=C(OC(F)(F)F)C=C3C=C2C(=O)NC=2C=C3C=CN(C)C3=CC=2)=C1 MEWNQVJSCZZUMB-UHFFFAOYSA-N 0.000 claims description 2
- NLGVAOXKERHLNB-UHFFFAOYSA-N n-(1-methylindol-5-yl)-1-[[3-(trifluoromethyl)phenyl]methyl]indole-2-carboxamide Chemical compound C=1C=C2N(C)C=CC2=CC=1NC(=O)C1=CC2=CC=CC=C2N1CC1=CC=CC(C(F)(F)F)=C1 NLGVAOXKERHLNB-UHFFFAOYSA-N 0.000 claims description 2
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- XEMBTFIOTUQYJX-UHFFFAOYSA-N 1-(3,4-dimethylphenyl)-n-(1-methylindol-5-yl)indole-2-carboxamide Chemical compound C1=C(C)C(C)=CC=C1N1C2=CC=CC=C2C=C1C(=O)NC1=CC=C(N(C)C=C2)C2=C1 XEMBTFIOTUQYJX-UHFFFAOYSA-N 0.000 claims 1
- LHAXLZHTJMEWSN-UHFFFAOYSA-N 1-(3,5-dimethylphenyl)-n-(1-methylindol-4-yl)indole-2-carboxamide Chemical compound CC1=CC(C)=CC(N2C3=CC=CC=C3C=C2C(=O)NC=2C=3C=CN(C)C=3C=CC=2)=C1 LHAXLZHTJMEWSN-UHFFFAOYSA-N 0.000 claims 1
- WRSHALSTTLXOBK-UHFFFAOYSA-N 1-(3,5-dimethylphenyl)-n-(1-methylindol-5-yl)indole-2-carboxamide Chemical compound CC1=CC(C)=CC(N2C3=CC=CC=C3C=C2C(=O)NC=2C=C3C=CN(C)C3=CC=2)=C1 WRSHALSTTLXOBK-UHFFFAOYSA-N 0.000 claims 1
- QEHWFOLQFKREGZ-UHFFFAOYSA-N 1-(3,5-dimethylphenyl)-n-(1-methylindol-6-yl)indole-2-carboxamide Chemical compound CC1=CC(C)=CC(N2C3=CC=CC=C3C=C2C(=O)NC=2C=C3N(C)C=CC3=CC=2)=C1 QEHWFOLQFKREGZ-UHFFFAOYSA-N 0.000 claims 1
- ANGVFZCMZZBOTL-UHFFFAOYSA-N 1-(3,5-dimethylphenyl)-n-(1-methylindol-7-yl)indole-2-carboxamide Chemical compound CC1=CC(C)=CC(N2C3=CC=CC=C3C=C2C(=O)NC=2C=3N(C)C=CC=3C=CC=2)=C1 ANGVFZCMZZBOTL-UHFFFAOYSA-N 0.000 claims 1
- DZSQBANJDKLFEQ-UHFFFAOYSA-N 1-(4-butan-2-ylphenyl)-n-(1-methylindol-5-yl)indole-2-carboxamide Chemical compound C1=CC(C(C)CC)=CC=C1N1C2=CC=CC=C2C=C1C(=O)NC1=CC=C(N(C)C=C2)C2=C1 DZSQBANJDKLFEQ-UHFFFAOYSA-N 0.000 claims 1
- ZBZXXQHUNVUFKB-UHFFFAOYSA-N 1-(4-chlorophenyl)-n-(1-methylindol-5-yl)indole-2-carboxamide Chemical compound C=1C=C2N(C)C=CC2=CC=1NC(=O)C1=CC2=CC=CC=C2N1C1=CC=C(Cl)C=C1 ZBZXXQHUNVUFKB-UHFFFAOYSA-N 0.000 claims 1
- BYVCNTTXPFCIAJ-UHFFFAOYSA-N 1-(4-cyclohexylphenyl)-n-(1-methylindol-5-yl)indole-2-carboxamide Chemical compound C=1C=C2N(C)C=CC2=CC=1NC(=O)C1=CC2=CC=CC=C2N1C(C=C1)=CC=C1C1CCCCC1 BYVCNTTXPFCIAJ-UHFFFAOYSA-N 0.000 claims 1
- BYOPYZVDBRXFDV-UHFFFAOYSA-N 1-(4-cyclopentylphenyl)-n-(1-methylindol-5-yl)indole-2-carboxamide Chemical compound C=1C=C2N(C)C=CC2=CC=1NC(=O)C1=CC2=CC=CC=C2N1C(C=C1)=CC=C1C1CCCC1 BYOPYZVDBRXFDV-UHFFFAOYSA-N 0.000 claims 1
- LLZIPBFFRVHYLK-UHFFFAOYSA-N 1-(4-ethoxyphenyl)-n-(1-methylindol-5-yl)indole-2-carboxamide Chemical compound C1=CC(OCC)=CC=C1N1C2=CC=CC=C2C=C1C(=O)NC1=CC=C(N(C)C=C2)C2=C1 LLZIPBFFRVHYLK-UHFFFAOYSA-N 0.000 claims 1
- SIPMYMRFSJXORU-UHFFFAOYSA-N 1-(4-tert-butylphenyl)-n-(1-methylindol-5-yl)indole-2-carboxamide Chemical compound C=1C=C2N(C)C=CC2=CC=1NC(=O)C1=CC2=CC=CC=C2N1C1=CC=C(C(C)(C)C)C=C1 SIPMYMRFSJXORU-UHFFFAOYSA-N 0.000 claims 1
- SPKYIDYOTSDFBP-UHFFFAOYSA-N 1-[(3-fluorophenyl)methyl]-4,6-dimethoxy-n-(1-methylindol-5-yl)indole-2-carboxamide Chemical compound C12=CC(OC)=CC(OC)=C2C=C(C(=O)NC=2C=C3C=CN(C)C3=CC=2)N1CC1=CC=CC(F)=C1 SPKYIDYOTSDFBP-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Public Health (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Virology (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Communicable Diseases (AREA)
- Reproductive Health (AREA)
- Psychiatry (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Endocrinology (AREA)
- Ophthalmology & Optometry (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0408652A FR2874015B1 (fr) | 2004-08-05 | 2004-08-05 | Derives de n-(1h-indolyl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique |
| PCT/FR2005/002014 WO2006024776A1 (fr) | 2004-08-05 | 2005-08-02 | Derives de n-(1 h-indolyl)-i h-ind0le-2-carb0xamides, leur preparation et leur application en therapeutique |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200700400A1 EA200700400A1 (ru) | 2007-06-29 |
| EA011714B1 true EA011714B1 (ru) | 2009-04-28 |
Family
ID=34950701
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200700400A EA011714B1 (ru) | 2004-08-05 | 2005-08-02 | Производные n-(1h-индолил)-1h-индол-2-карбоксамидов, их получение и их применение в терапии |
Country Status (37)
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2874015B1 (fr) * | 2004-08-05 | 2006-09-15 | Sanofi Synthelabo | Derives de n-(1h-indolyl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique |
| FR2880625B1 (fr) | 2005-01-07 | 2007-03-09 | Sanofi Aventis Sa | Derives de n-(heteroaryl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique |
| FR2888847B1 (fr) | 2005-07-22 | 2007-08-31 | Sanofi Aventis Sa | Derives de n-(heteriaryl)-1-heteorarylalkyl-1h-indole-2- carboxamides, leur preparation et application en therapeutique |
| PE20080145A1 (es) | 2006-03-21 | 2008-02-11 | Janssen Pharmaceutica Nv | Tetrahidro-pirimidoazepinas como moduladores de trpv1 |
| FR2910473B1 (fr) | 2006-12-26 | 2009-02-13 | Sanofi Aventis Sa | Derives de n-(amino-heteroaryl)-1h-pyrrolopyridine-2- carboxamides, leur preparation et leur application en therapeutique. |
| FR2911604B1 (fr) * | 2007-01-19 | 2009-04-17 | Sanofi Aventis Sa | Derives de n-(heteroaryl-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique |
| EP2185560A4 (en) * | 2007-08-10 | 2011-10-05 | Lundbeck & Co As H | HETEROARYLAMIDE ANALOGS |
| JP5562865B2 (ja) | 2007-12-17 | 2014-07-30 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | Ｔｒｐｖ１のイミダゾロ−、オキサゾロ−、及びチアゾロピリミジン・モジュレーター |
| FR2926556B1 (fr) * | 2008-01-22 | 2010-02-19 | Sanofi Aventis | Derives de carboxamides n-azabicycliques, leur preparation et leur application en therapeutique |
| FR2926554B1 (fr) | 2008-01-22 | 2010-03-12 | Sanofi Aventis | Derives de carboxamides azabicycliques, leur preparation et leur application en therapeutique |
| FR2926555B1 (fr) * | 2008-01-22 | 2010-02-19 | Sanofi Aventis | Derives bicycliques de carboxamides azabicycliques, leur preparation et leur application en therapeutique |
| US20100210682A1 (en) * | 2009-02-19 | 2010-08-19 | Abbott Laboratories | Repeated Dosing of TRPV1 Antagonists |
| FR3007850B1 (fr) | 2013-06-28 | 2015-07-17 | Probayes | Systeme de prediction de temperature |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003049702A2 (en) * | 2001-12-10 | 2003-06-19 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
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| US5846990A (en) * | 1995-07-24 | 1998-12-08 | Bristol-Myers Squibb Co. | Substituted biphenyl isoxazole sulfonamides |
| ES2259803T3 (es) * | 1996-02-13 | 2006-10-16 | Abbott Laboratories | Nuevos derivados de pirrolidina sustituidos con benzo-1,3-dioxolilo y benzofuranilo como antagonistas de endostelina. |
| HUP0003484A3 (en) * | 1997-08-04 | 2002-02-28 | Abbott Lab | Pyrrolidine-3-crboxylic acid derivatives and their use as endothelin antagonists |
| EP1314733A1 (en) * | 2001-11-22 | 2003-05-28 | Aventis Pharma Deutschland GmbH | Indole-2-carboxamides as factor Xa inhibitors |
| JP2005531574A (ja) * | 2002-05-22 | 2005-10-20 | アムジエン・インコーポレーテツド | 痛みの治療にバニロイド受容体リガンドとして使用するためのアミノ−ピリジン、−ピリジンおよびピリダジン誘導体 |
| JP2006511562A (ja) * | 2002-12-20 | 2006-04-06 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | 泌尿器系疾患の処置のための置換２，５−ジアミドインドール類の使用 |
| US7531558B2 (en) | 2003-02-14 | 2009-05-12 | Glaxo Group Limited | Carboxamide derivatives |
| US7544803B2 (en) * | 2004-01-23 | 2009-06-09 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
| FR2874015B1 (fr) * | 2004-08-05 | 2006-09-15 | Sanofi Synthelabo | Derives de n-(1h-indolyl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique |
| FR2880625B1 (fr) * | 2005-01-07 | 2007-03-09 | Sanofi Aventis Sa | Derives de n-(heteroaryl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique |
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Designated state(s): AM AZ BY KZ KG MD TJ TM RU |