DE60203529T2 - Indolderivate als cox-ii-inhibitoren - Google Patents
Indolderivate als cox-ii-inhibitoren Download PDFInfo
- Publication number
- DE60203529T2 DE60203529T2 DE60203529T DE60203529T DE60203529T2 DE 60203529 T2 DE60203529 T2 DE 60203529T2 DE 60203529 T DE60203529 T DE 60203529T DE 60203529 T DE60203529 T DE 60203529T DE 60203529 T2 DE60203529 T2 DE 60203529T2
- Authority
- DE
- Germany
- Prior art keywords
- alkyl
- group
- methanesulfonyl
- indole
- compound
- 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.)
- Expired - Fee Related
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- 239000003112 inhibitor Substances 0.000 title claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 126
- 125000000217 alkyl group Chemical group 0.000 claims description 65
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 34
- 238000000034 method Methods 0.000 claims description 34
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 201000010099 disease Diseases 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 19
- 125000005843 halogen group Chemical group 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 15
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 15
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- XAOIOAYWZAVEIW-UHFFFAOYSA-N 3-(2,4-difluorophenyl)sulfanyl-6-methylsulfonyl-1h-indole-2-carbonitrile Chemical compound N#CC=1NC2=CC(S(=O)(=O)C)=CC=C2C=1SC1=CC=C(F)C=C1F XAOIOAYWZAVEIW-UHFFFAOYSA-N 0.000 claims description 6
- VHSYYXRBWBHMNB-UHFFFAOYSA-N 3-(4-fluorophenoxy)-2-methyl-6-methylsulfonyl-1h-indole Chemical compound CC=1NC2=CC(S(C)(=O)=O)=CC=C2C=1OC1=CC=C(F)C=C1 VHSYYXRBWBHMNB-UHFFFAOYSA-N 0.000 claims description 6
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- GVUYJYPBPIQKHW-UHFFFAOYSA-N (6-methylsulfonyl-3-phenylsulfanyl-1h-indol-2-yl)methanol Chemical compound OCC=1NC2=CC(S(=O)(=O)C)=CC=C2C=1SC1=CC=CC=C1 GVUYJYPBPIQKHW-UHFFFAOYSA-N 0.000 claims description 5
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- OHVHHRUUBCGBLX-UHFFFAOYSA-N 3-(4-fluorophenyl)sulfanyl-6-methylsulfonyl-1h-indole-2-carbonitrile Chemical compound N#CC=1NC2=CC(S(=O)(=O)C)=CC=C2C=1SC1=CC=C(F)C=C1 OHVHHRUUBCGBLX-UHFFFAOYSA-N 0.000 claims description 4
- VNYCGFXZOQHLEM-UHFFFAOYSA-N 3-(4-fluorophenyl)sulfinyl-2-methyl-6-methylsulfonyl-1h-indole Chemical compound CC=1NC2=CC(S(C)(=O)=O)=CC=C2C=1S(=O)C1=CC=C(F)C=C1 VNYCGFXZOQHLEM-UHFFFAOYSA-N 0.000 claims description 4
- JGGHRZWTRXUNBK-UHFFFAOYSA-N 3-[(2-chlorophenyl)methyl]-2-methyl-6-methylsulfonyl-1h-indole Chemical compound CC=1NC2=CC(S(C)(=O)=O)=CC=C2C=1CC1=CC=CC=C1Cl JGGHRZWTRXUNBK-UHFFFAOYSA-N 0.000 claims description 4
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- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 2
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- 239000000243 solution Substances 0.000 description 24
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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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/06—Antiabortive agents; Labour repressants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
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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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
-
- 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
-
- 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
- C07D209/32—Oxygen atoms
- C07D209/36—Oxygen atoms in position 3, e.g. adrenochrome
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Psychiatry (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US32538901P | 2001-09-27 | 2001-09-27 | |
| US325389P | 2001-09-27 | ||
| PCT/EP2002/010557 WO2003029212A1 (en) | 2001-09-27 | 2002-09-20 | Indole derivatives as cox ii inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60203529D1 DE60203529D1 (de) | 2005-05-04 |
| DE60203529T2 true DE60203529T2 (de) | 2006-03-16 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60203529T Expired - Fee Related DE60203529T2 (de) | 2001-09-27 | 2002-09-20 | Indolderivate als cox-ii-inhibitoren |
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|---|---|
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| EP (1) | EP1438289B1 (enExample) |
| JP (1) | JP4141954B2 (enExample) |
| KR (1) | KR20040047862A (enExample) |
| CN (1) | CN1261412C (enExample) |
| AR (1) | AR036624A1 (enExample) |
| AT (1) | ATE292115T1 (enExample) |
| BR (1) | BR0212925A (enExample) |
| CA (1) | CA2461670A1 (enExample) |
| CO (1) | CO5560557A2 (enExample) |
| DE (1) | DE60203529T2 (enExample) |
| DK (1) | DK1438289T3 (enExample) |
| ES (1) | ES2238616T3 (enExample) |
| HR (1) | HRPK20040271B3 (enExample) |
| HU (1) | HUP0401499A3 (enExample) |
| IL (1) | IL160752A0 (enExample) |
| MX (1) | MXPA04002824A (enExample) |
| NO (1) | NO20041237L (enExample) |
| NZ (1) | NZ531577A (enExample) |
| PL (1) | PL370342A1 (enExample) |
| PT (1) | PT1438289E (enExample) |
| RU (1) | RU2004113111A (enExample) |
| SI (1) | SI1438289T1 (enExample) |
| WO (1) | WO2003029212A1 (enExample) |
| ZA (1) | ZA200402360B (enExample) |
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| DE60203529T2 (de) * | 2001-09-27 | 2006-03-16 | F. Hoffmann-La Roche Ag | Indolderivate als cox-ii-inhibitoren |
| SE0202241D0 (sv) * | 2002-07-17 | 2002-07-17 | Astrazeneca Ab | Novel Compounds |
| US7365090B2 (en) * | 2002-08-07 | 2008-04-29 | Idenix Pharmaceuticals, Inc. | Substituted phenylindoles for the treatment of HIV |
| US20050250794A1 (en) * | 2003-12-19 | 2005-11-10 | Andrew Napper | Methods of treating a disorder |
| US7119214B2 (en) | 2004-04-13 | 2006-10-10 | Cephalon France | Thio-substituted tricyclic and bicyclic aromatic methanesulfinyl derivatives |
| US7423176B2 (en) | 2004-04-13 | 2008-09-09 | Cephalon, Inc. | Bicyclic aromatic sulfinyl derivatives |
| EP1589016A1 (en) * | 2004-04-13 | 2005-10-26 | Cephalon France | Thio-substituted tricyclic and bicyclic aromatic methanesulfinyl derivatives |
| CN101006053A (zh) | 2004-06-18 | 2007-07-25 | 比奥里波克斯公司 | 用于治疗炎症的吲哚 |
| WO2006041961A1 (en) * | 2004-10-05 | 2006-04-20 | GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTHAND HUMAN SERVICES | Arylthioindole tubulin polymerization inhibitors and methods of treating or preventing cancer using same |
| AU2005325497A1 (en) | 2005-01-19 | 2006-07-27 | Biolipox Ab | Indoles useful in the treatment of inflammation |
| US7622495B2 (en) * | 2006-10-03 | 2009-11-24 | Neurim Pharmaceuticals (1991) Ltd. | Substituted aryl-indole compounds and their kynurenine/kynuramine-like metabolites as therapeutic agents |
| CA2668959A1 (en) | 2006-11-09 | 2008-05-15 | F. Hoffmann-La Roche Ag | Indole and benzofuran 2-carboxamide derivatives |
| JP2013536200A (ja) | 2010-08-20 | 2013-09-19 | アミラ ファーマシューティカルス，インコーポレーテッド | オートタキシン阻害剤およびその使用 |
| EP2714680B1 (en) | 2011-05-27 | 2015-11-25 | Amira Pharmaceuticals, Inc. | Heterocyclic autotaxin inhibitors and uses thereof |
| WO2015042053A1 (en) | 2013-09-17 | 2015-03-26 | Pharmakea, Inc. | Vinyl autotaxin inhibitor compounds |
| US9951026B2 (en) | 2013-09-17 | 2018-04-24 | Pharmakea, Inc. | Heterocyclic vinyl autotaxin inhibitor compounds |
| US9850203B2 (en) | 2013-09-26 | 2017-12-26 | Pharmakea, Inc. | Autotaxin inhibitor compounds |
| WO2015077503A1 (en) | 2013-11-22 | 2015-05-28 | Pharmakea, Inc. | Autotaxin inhibitor compounds |
| AU2016268250B2 (en) | 2015-05-27 | 2020-08-27 | Sabre Therapeutics Llc | Autotaxin inhibitors and uses thereof |
| KR102241064B1 (ko) | 2019-07-30 | 2021-04-16 | 부산대학교 산학협력단 | 신규한 인돌 유도체 및 이를 포함하는 염증성 질환 예방 또는 치료용 조성물 |
| CN113004187B (zh) * | 2021-03-16 | 2022-09-20 | 沈阳药科大学 | 一种具有抑制有机阴离子转运体1活性的化合物及制备方法和应用 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4654360A (en) * | 1984-06-01 | 1987-03-31 | Syntex (U.S.A.) Inc. | 1,2,3-trisubstituted indoles for treatment of inflammation |
| JPH0347123A (ja) | 1989-05-05 | 1991-02-28 | G D Searle & Co | インドール―２―カルボキシレート化合物類を含有するｃｎｓ疾患治療用組成物 |
| DE4338770A1 (de) | 1993-11-12 | 1995-05-18 | Matthias Dr Lehr | Indol-2-alkansäuren und ihre Derivate als Hemmstoffe der Phospholipase A¶2¶ |
| WO1998008818A1 (en) | 1996-08-26 | 1998-03-05 | Genetics Institute, Inc. | Inhibitors of phospholipase enzymes |
| WO1998051667A1 (en) * | 1997-05-16 | 1998-11-19 | Chugai Seiyaku Kabushiki Kaisha | Indole derivatives and mono- and diazaindole derivatives |
| EP1062216A1 (en) | 1998-02-25 | 2000-12-27 | Genetics Institute, Inc. | Inhibitors of phospholipase a2 |
| MXPA00006605A (es) * | 1999-07-02 | 2004-12-09 | Pfizer | Compuestos de carbonil-indol biciclicos como agentes antiinflamatorios/analgesicos. |
| US6306890B1 (en) * | 1999-08-30 | 2001-10-23 | Vanderbilt University | Esters derived from indolealkanols and novel amides derived from indolealkylamides that are selective COX-2 inhibitors |
| US6376708B1 (en) * | 2000-04-11 | 2002-04-23 | Monsanto Technology Llc | Process and catalyst for dehydrogenating primary alcohols to make carboxylic acid salts |
| DE60203529T2 (de) * | 2001-09-27 | 2006-03-16 | F. Hoffmann-La Roche Ag | Indolderivate als cox-ii-inhibitoren |
| TW200400177A (en) * | 2002-06-04 | 2004-01-01 | Wyeth Corp | 1-(Aminoalkyl)-3-sulfonylindole and-indazole derivatives as 5-hydroxytryptamine-6 ligands |
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