DE60105195T2 - Benzofuran- und benzothiophen-derivative als selektive cox-2 inhibitoren - Google Patents
Benzofuran- und benzothiophen-derivative als selektive cox-2 inhibitoren Download PDFInfo
- Publication number
- DE60105195T2 DE60105195T2 DE60105195T DE60105195T DE60105195T2 DE 60105195 T2 DE60105195 T2 DE 60105195T2 DE 60105195 T DE60105195 T DE 60105195T DE 60105195 T DE60105195 T DE 60105195T DE 60105195 T2 DE60105195 T2 DE 60105195T2
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- Prior art keywords
- alkyl
- compound
- formula
- carbonitrile
- thiophene
- Prior art date
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- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical class C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 title description 9
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 title description 5
- 229940111134 coxibs Drugs 0.000 title description 4
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 99
- 125000000217 alkyl group Chemical group 0.000 claims description 65
- -1 cyano, hydroxy Chemical group 0.000 claims description 55
- 239000000203 mixture Substances 0.000 claims description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 13
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- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
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- MVWPDJHXDFYOBO-UHFFFAOYSA-N 3-(2-chlorophenyl)sulfanyl-6-methylsulfonyl-1-benzothiophene-2-carbonitrile Chemical compound N#CC=1SC2=CC(S(=O)(=O)C)=CC=C2C=1SC1=CC=CC=C1Cl MVWPDJHXDFYOBO-UHFFFAOYSA-N 0.000 claims description 2
- QLQJYIFVJNQHDY-UHFFFAOYSA-N 3-(2-fluorophenyl)sulfanyl-6-methylsulfonyl-1-benzothiophene-2-carbonitrile Chemical compound N#CC=1SC2=CC(S(=O)(=O)C)=CC=C2C=1SC1=CC=CC=C1F QLQJYIFVJNQHDY-UHFFFAOYSA-N 0.000 claims description 2
- XPOSOACFOVKIOF-UHFFFAOYSA-N 3-(4-chloro-2-fluorophenoxy)-6-methylsulfonyl-1-benzothiophene-2-carbonitrile Chemical compound N#CC=1SC2=CC(S(=O)(=O)C)=CC=C2C=1OC1=CC=C(Cl)C=C1F XPOSOACFOVKIOF-UHFFFAOYSA-N 0.000 claims description 2
- VCXFSUIHWSMGJO-UHFFFAOYSA-N 3-(4-ethoxyphenoxy)-6-methylsulfonyl-1-benzothiophene-2-carbonitrile Chemical compound C1=CC(OCC)=CC=C1OC1=C(C#N)SC2=CC(S(C)(=O)=O)=CC=C12 VCXFSUIHWSMGJO-UHFFFAOYSA-N 0.000 claims description 2
- WXEANUYPVQMIDM-UHFFFAOYSA-N 3-(4-fluorophenyl)sulfanyl-6-methylsulfonyl-1-benzothiophene-2-carbonitrile Chemical compound N#CC=1SC2=CC(S(=O)(=O)C)=CC=C2C=1SC1=CC=C(F)C=C1 WXEANUYPVQMIDM-UHFFFAOYSA-N 0.000 claims description 2
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
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- 238000005481 NMR spectroscopy Methods 0.000 description 7
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D307/84—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A—HUMAN NECESSITIES
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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
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- A61P25/06—Antimigraine agents
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D333/70—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
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- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Psychiatry (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Immunology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25128300P | 2000-12-05 | 2000-12-05 | |
| US251283P | 2000-12-05 | ||
| PCT/EP2001/013716 WO2002046178A2 (en) | 2000-12-05 | 2001-11-26 | Benzofuran and benzothiophene derivatives as selective cox-2 inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60105195D1 DE60105195D1 (de) | 2004-09-30 |
| DE60105195T2 true DE60105195T2 (de) | 2005-09-08 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60105195T Expired - Fee Related DE60105195T2 (de) | 2000-12-05 | 2001-11-26 | Benzofuran- und benzothiophen-derivative als selektive cox-2 inhibitoren |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US6433005B1 (enExample) |
| EP (1) | EP1347963B1 (enExample) |
| JP (1) | JP4212892B2 (enExample) |
| KR (1) | KR20030070054A (enExample) |
| CN (1) | CN1273460C (enExample) |
| AR (1) | AR035719A1 (enExample) |
| AT (1) | ATE274507T1 (enExample) |
| AU (2) | AU2002224890B2 (enExample) |
| BR (1) | BR0115963A (enExample) |
| CA (1) | CA2437048A1 (enExample) |
| DE (1) | DE60105195T2 (enExample) |
| ES (1) | ES2225641T3 (enExample) |
| MX (1) | MXPA03004398A (enExample) |
| PT (1) | PT1347963E (enExample) |
| WO (1) | WO2002046178A2 (enExample) |
| ZA (1) | ZA200303641B (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999051587A1 (en) * | 1998-04-01 | 1999-10-14 | Ono Pharmaceutical Co., Ltd. | Fused thiophene derivatives and drugs containing the same as the active ingredient |
| JP2001261674A (ja) * | 2000-03-22 | 2001-09-26 | Mitsui Chemicals Inc | ベンゾチオフェン誘導体およびそれを有効成分として含有する核内レセプター作動薬 |
| AU5878001A (en) * | 2000-05-18 | 2001-11-26 | Daiichi Pharmaceutical Co., Ltd. | Novel benzothiophene derivatives |
| AU2001268051A1 (en) * | 2000-06-28 | 2002-01-08 | Eli Lilly And Company | Spla2 inhibitors |
| US7071220B2 (en) * | 2000-09-18 | 2006-07-04 | Toa Eiyo Ltd. | N-substituted benzothiophenesulfonamide derivatives |
| WO2005033112A2 (en) * | 2003-10-02 | 2005-04-14 | Cephalon, Inc. | Substituted indole derivatives |
| ATE555091T1 (de) | 2006-02-03 | 2012-05-15 | Bionomics Ltd | Substituierte benzofurane, benzothiophene, benzoselenophene und indole und ihre verwendung als tubulinpolymerisationsinhibitoren |
| WO2008055808A1 (en) | 2006-11-09 | 2008-05-15 | F. Hoffmann-La Roche Ag | Indole and benzofuran 2-carboxamide derivatives |
| AU2011202542A1 (en) | 2010-07-14 | 2012-02-02 | Indian Institute Of Science | Benzothiophene carboxamide compounds, composition and applications thereof |
| CN103819371B (zh) * | 2012-11-16 | 2016-05-04 | 中国科学院大连化学物理研究所 | 一种对甲砜基苯甲醛的合成方法 |
| CN103058988B (zh) * | 2012-12-31 | 2015-09-02 | 中国人民大学 | 苯并噻吩及其衍生物及其制备方法与应用 |
| CN110903225B (zh) * | 2019-12-11 | 2021-11-09 | 苏州开元民生科技股份有限公司 | 一种对甲砜基苯甲醛的合成方法 |
| CN114456136B (zh) * | 2022-01-27 | 2024-06-07 | 广西中医药大学 | 双靶点非甾体抗炎化合物及其制备方法与用途 |
| KR102542698B1 (ko) * | 2022-04-05 | 2023-06-14 | 주식회사 베노바이오 | 신규한 벤조사이오펜 유도체 및 bet 억제제로서의 용도 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3331854A (en) * | 1964-12-14 | 1967-07-18 | American Cyanamid Co | Novel furan and thiophene compounds |
| US4663347A (en) | 1983-10-31 | 1987-05-05 | Merck Frosst Canada, Inc. | Benzofuran 2-carboxylic acid esters useful as inhibitors of leukotriene biosynthesis |
| US4745127A (en) * | 1983-10-31 | 1988-05-17 | Merck Frosst Canada, Inc. | Benzyl esters of benzofuran-2-carboxylic acids useful as inhibitors of leukotriene biosynthesis |
| US4822803A (en) | 1983-10-31 | 1989-04-18 | Merck Frosst Canada, Inc. | Benzofuran 2-carboxylic acid hydrazides useful as inhibitors of leukotriene biosynthesis |
| US4933351A (en) | 1983-10-31 | 1990-06-12 | Merck Frosst Canada, Inc. | Benzofuran 2-carbox amides useful as inhibitors of leukoriene biosynthesis |
| DE3342624A1 (de) | 1983-11-25 | 1984-03-29 | Heinfried Dr. 4019 Monheim Grote | Benzaronderivate, verfahren zu ihrer herstellung und diese derivate enthaltende arzneimittel |
| US4621091A (en) | 1984-10-09 | 1986-11-04 | Merck & Co., Inc. | 3-hydroxybenzo[b]thiophene-2-sulfide derivatives compositions, and method of use therefor |
| US5208253A (en) * | 1992-02-24 | 1993-05-04 | Warner-Lambert Company | 3-alkyloxy-, aryloxy-, or arylalkyloxy-benzo(b) thiophene-2-carboxamides as inhibitors of cell adhesion |
| WO1995002406A2 (en) | 1993-07-15 | 1995-01-26 | Warner-Lambert Company | Use of benzothiophenes and benzofurans for the treatment of inflammatory bowel disease and inflammation assay method |
| US5426113A (en) | 1994-04-08 | 1995-06-20 | Warner-Lambert Company | Method of preventing ulcer formation caused by nonsteroidal antiinflammatory drugs employing tetrazol-benzothiophene carboxamide compounds |
| US5521213A (en) * | 1994-08-29 | 1996-05-28 | Merck Frosst Canada, Inc. | Diaryl bicyclic heterocycles as inhibitors of cyclooxygenase-2 |
| CN1211921A (zh) * | 1996-02-22 | 1999-03-24 | 伊莱利利公司 | 苯并噻吩、含有它们的制剂及其制备方法 |
| US5731342A (en) | 1996-02-22 | 1998-03-24 | Eli Lilly And Company | Benzothiophenes, formulations containing same, and methods |
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2001
- 2001-11-26 KR KR10-2003-7007600A patent/KR20030070054A/ko not_active Abandoned
- 2001-11-26 MX MXPA03004398A patent/MXPA03004398A/es active IP Right Grant
- 2001-11-26 PT PT01994723T patent/PT1347963E/pt unknown
- 2001-11-26 DE DE60105195T patent/DE60105195T2/de not_active Expired - Fee Related
- 2001-11-26 AT AT01994723T patent/ATE274507T1/de not_active IP Right Cessation
- 2001-11-26 CA CA002437048A patent/CA2437048A1/en not_active Abandoned
- 2001-11-26 WO PCT/EP2001/013716 patent/WO2002046178A2/en not_active Ceased
- 2001-11-26 AU AU2002224890A patent/AU2002224890B2/en not_active Ceased
- 2001-11-26 BR BR0115963-1A patent/BR0115963A/pt not_active IP Right Cessation
- 2001-11-26 ES ES01994723T patent/ES2225641T3/es not_active Expired - Lifetime
- 2001-11-26 JP JP2002547917A patent/JP4212892B2/ja not_active Expired - Fee Related
- 2001-11-26 CN CNB01820077XA patent/CN1273460C/zh not_active Expired - Fee Related
- 2001-11-26 AU AU2489002A patent/AU2489002A/xx active Pending
- 2001-11-26 EP EP01994723A patent/EP1347963B1/en not_active Expired - Lifetime
- 2001-12-03 US US10/006,349 patent/US6433005B1/en not_active Expired - Fee Related
- 2001-12-03 AR ARP010105603A patent/AR035719A1/es not_active Application Discontinuation
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2003
- 2003-05-12 ZA ZA200303641A patent/ZA200303641B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20020107280A1 (en) | 2002-08-08 |
| EP1347963B1 (en) | 2004-08-25 |
| WO2002046178A2 (en) | 2002-06-13 |
| CN1479736A (zh) | 2004-03-03 |
| EP1347963A2 (en) | 2003-10-01 |
| US6433005B1 (en) | 2002-08-13 |
| AR035719A1 (es) | 2004-07-07 |
| AU2489002A (en) | 2002-06-18 |
| DE60105195D1 (de) | 2004-09-30 |
| BR0115963A (pt) | 2003-10-28 |
| ZA200303641B (en) | 2004-08-12 |
| CA2437048A1 (en) | 2002-06-13 |
| ATE274507T1 (de) | 2004-09-15 |
| CN1273460C (zh) | 2006-09-06 |
| JP4212892B2 (ja) | 2009-01-21 |
| JP2004517088A (ja) | 2004-06-10 |
| PT1347963E (pt) | 2004-12-31 |
| WO2002046178A3 (en) | 2002-10-10 |
| ES2225641T3 (es) | 2005-03-16 |
| KR20030070054A (ko) | 2003-08-27 |
| MXPA03004398A (es) | 2003-09-05 |
| AU2002224890B2 (en) | 2007-03-22 |
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