CA2091058A1 - Methylen-oxindole derivatives and process for their preparation - Google Patents
Methylen-oxindole derivatives and process for their preparationInfo
- Publication number
- CA2091058A1 CA2091058A1 CA002091058A CA2091058A CA2091058A1 CA 2091058 A1 CA2091058 A1 CA 2091058A1 CA 002091058 A CA002091058 A CA 002091058A CA 2091058 A CA2091058 A CA 2091058A CA 2091058 A1 CA2091058 A1 CA 2091058A1
- Authority
- CA
- Canada
- Prior art keywords
- hydrogen
- alkyl
- methylen
- halogen
- preparation
- 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.)
- Granted
Links
Classifications
-
- 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
- C07D403/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D209/34—Oxygen atoms in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Abstract
The invention provides new methylen-indole derivatives of formula (I), wherein R is a group (a) in which R4 is hydrogen, hydroxy, C1-C6 alkoxy, C2-C6 alkanoyloxy, carboxy, nitro or NHR7, wherein R7 is hydrogen or C1-C6 alkyl; R5 is hydrogen, C1-C6 alkyl or halogen; and R6 is hydrogen or C1-C6 alkyl; n is zero, 1 or 2;
R1 is hydrogen, C1-C6 alkyl or C2-C6 alkanoyl;
R2 is hydrogen, C1-C6 alkyl, halogen, cyano, carboxyl, nitro or -NHR7 in which R7 is as defined above; R3 is hydrogen, C1-C6 alkyl or C2-C6 alkanoyl; and the pharmaceutically acceptable salts thereof; and wherein, when, at the same time, R2 is hydrogen, C1-C6 alkyl, halogen or cyano and R3 is hydrogen, R1 and n being as defined above, then at least one of R4, R5 and R6 is other than hydrogen, which are useful as tyrosine kinase inhibitors.
R1 is hydrogen, C1-C6 alkyl or C2-C6 alkanoyl;
R2 is hydrogen, C1-C6 alkyl, halogen, cyano, carboxyl, nitro or -NHR7 in which R7 is as defined above; R3 is hydrogen, C1-C6 alkyl or C2-C6 alkanoyl; and the pharmaceutically acceptable salts thereof; and wherein, when, at the same time, R2 is hydrogen, C1-C6 alkyl, halogen or cyano and R3 is hydrogen, R1 and n being as defined above, then at least one of R4, R5 and R6 is other than hydrogen, which are useful as tyrosine kinase inhibitors.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB919115160A GB9115160D0 (en) | 1991-07-12 | 1991-07-12 | Methylen-oxindole derivatives and process for their preparation |
GB9115160.5 | 1991-07-12 | ||
PCT/EP1992/001569 WO1993001182A1 (en) | 1991-07-12 | 1992-07-10 | Methylen-oxindole derivatives and process for their preparation |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2091058A1 true CA2091058A1 (en) | 1993-01-13 |
CA2091058C CA2091058C (en) | 2004-03-30 |
Family
ID=10698323
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002091058A Expired - Fee Related CA2091058C (en) | 1991-07-12 | 1992-07-10 | Methylen-oxindole derivatives and process for their preparation |
Country Status (22)
Country | Link |
---|---|
US (1) | US5409949A (en) |
EP (2) | EP0552329B1 (en) |
JP (1) | JP3188701B2 (en) |
KR (1) | KR930702337A (en) |
AT (1) | ATE206420T1 (en) |
AU (1) | AU656015B2 (en) |
CA (1) | CA2091058C (en) |
DE (1) | DE69232093T2 (en) |
DK (1) | DK0552329T3 (en) |
ES (1) | ES2165357T3 (en) |
FI (1) | FI931061A0 (en) |
GB (1) | GB9115160D0 (en) |
HU (1) | HUT67496A (en) |
IE (1) | IE922253A1 (en) |
IL (1) | IL102383A (en) |
MX (1) | MX9204008A (en) |
NZ (1) | NZ243454A (en) |
PT (1) | PT552329E (en) |
RU (1) | RU2072989C1 (en) |
TW (1) | TW202444B (en) |
WO (1) | WO1993001182A1 (en) |
ZA (1) | ZA925169B (en) |
Families Citing this family (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9004483D0 (en) * | 1990-02-28 | 1990-04-25 | Erba Carlo Spa | New aryl-and heteroarylethenylene derivatives and process for their preparation |
US5587385A (en) * | 1991-12-24 | 1996-12-24 | Farmitalia Carlo Erba S.R.L. | Arylidene-heterocyclic derivatives and process for their preparation |
GB9313638D0 (en) * | 1993-07-01 | 1993-08-18 | Erba Carlo Spa | Arylidene and heteroarylidene oxindole derivatives and process for their preparation |
GB9326136D0 (en) * | 1993-12-22 | 1994-02-23 | Erba Carlo Spa | Biologically active 3-substituted oxindole derivatives useful as anti-angiogenic agents |
GB9406137D0 (en) * | 1994-03-28 | 1994-05-18 | Erba Carlo Spa | N-substituted beta-aryl- and betaheteroaryl-alpha-cyanoacrylamide derivatives and process for their preparation |
GB9412719D0 (en) * | 1994-06-24 | 1994-08-17 | Erba Carlo Spa | Substituted azaindolylidene compounds and process for their preparation |
GB9501567D0 (en) * | 1995-01-26 | 1995-03-15 | Pharmacia Spa | Hydrosoluble 3-arylidene-2-oxindole derivatives as tyrosine kinase inhibitors |
GB9507298D0 (en) * | 1995-04-07 | 1995-05-31 | Pharmacia Spa | Substituted indolylmethylene-oxindale analogues as tyrosine kinase inhibitors |
US5880141A (en) * | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
US6147106A (en) | 1997-08-20 | 2000-11-14 | Sugen, Inc. | Indolinone combinatorial libraries and related products and methods for the treatment of disease |
US6906093B2 (en) | 1995-06-07 | 2005-06-14 | Sugen, Inc. | Indolinone combinatorial libraries and related products and methods for the treatment of disease |
GB9610964D0 (en) * | 1996-05-24 | 1996-07-31 | Pharmacia & Upjohn Spa | Substituted tetralylmethylen-oxindole analogues as tyrosine kinase inhibitors |
AU4155697A (en) * | 1996-08-23 | 1998-03-06 | Sugen, Inc. | Indolinone combinatorial libraries and related products and methods for the treatment of disease |
AU7622698A (en) * | 1996-12-05 | 1998-06-29 | Sugen, Inc. | Use of indolinone compounds as modulators of protein kinases |
US6051597A (en) * | 1997-06-13 | 2000-04-18 | Merck & Co., Inc. | Indolylquinones as antidiabetic agents |
US20040067531A1 (en) * | 1997-08-20 | 2004-04-08 | Sugen, Inc. | Methods of modulating protein tyrosine kinase function with substituted indolinone compounds |
GB9718913D0 (en) | 1997-09-05 | 1997-11-12 | Glaxo Group Ltd | Substituted oxindole derivatives |
US6531502B1 (en) | 1998-01-21 | 2003-03-11 | Sugen, Inc. | 3-Methylidenyl-2-indolinone modulators of protein kinase |
AU760046B2 (en) | 1998-02-27 | 2003-05-08 | United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Disubstituted lavendustin a analogs and pharmaceutical compositions comprising the analogs |
US6102942A (en) | 1998-03-30 | 2000-08-15 | Endovascular Technologies, Inc. | Stent/graft deployment catheter with a stent/graft attachment mechanism |
US6569868B2 (en) | 1998-04-16 | 2003-05-27 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
AU5468499A (en) * | 1998-08-04 | 2000-02-28 | Sugen, Inc. | 3-methylidenyl-2-indolinone modulators of protein kinase |
US6680335B2 (en) | 1998-09-28 | 2004-01-20 | Sugen, Inc. | Methods of modulating protein tyrosine kinase function with substituted indolinone compounds |
AU760039B2 (en) | 1998-12-17 | 2003-05-08 | F. Hoffmann-La Roche Ag | 4-aryloxindoles as inhibitors of JNK protein kinases |
BR9916324A (en) | 1998-12-17 | 2001-10-02 | Hoffmann La Roche | 4,5-pyrazinoxindoles as protein kinase inhibitors |
US6153634A (en) * | 1998-12-17 | 2000-11-28 | Hoffmann-La Roche Inc. | 4,5-azolo-oxindoles |
KR100649925B1 (en) | 1998-12-17 | 2007-02-28 | 에프. 호프만-라 로슈 아게 | 4-alkenyl and alkynyl oxindoles as inhibitors of cyclin-dependent kinases, in particular cdk2 |
JP2000247949A (en) * | 1999-02-26 | 2000-09-12 | Eisai Co Ltd | Indole compound containing sulfonamide |
GB9904933D0 (en) | 1999-03-04 | 1999-04-28 | Glaxo Group Ltd | Compounds |
US6492398B1 (en) | 1999-03-04 | 2002-12-10 | Smithkline Beechman Corporation | Thiazoloindolinone compounds |
US6624171B1 (en) | 1999-03-04 | 2003-09-23 | Smithkline Beecham Corporation | Substituted aza-oxindole derivatives |
CA2368041A1 (en) * | 1999-03-24 | 2000-09-28 | Sugen, Inc. | Indolinone compounds as kinase inhibitors |
US6689806B1 (en) | 1999-03-24 | 2004-02-10 | Sugen, Inc. | Indolinone compounds as kinase inhibitors |
US6878733B1 (en) | 1999-11-24 | 2005-04-12 | Sugen, Inc. | Formulations for pharmaceutical agents ionizable as free acids or free bases |
US6313310B1 (en) | 1999-12-15 | 2001-11-06 | Hoffmann-La Roche Inc. | 4-and 5-alkynyloxindoles and 4-and 5-alkenyloxindoles |
CA2399001C (en) | 2000-02-03 | 2010-07-20 | Eisai Co., Ltd. | Integrin expression inhibitor |
ES2290117T3 (en) * | 2000-02-15 | 2008-02-16 | Sugen, Inc. | PROTEIN QUINASE 2-INDOLIN INHIBITORS REPLACED WITH PIRROL. |
US6620818B1 (en) | 2000-03-01 | 2003-09-16 | Smithkline Beecham Corporation | Method for reducing the severity of side effects of chemotherapy and/or radiation therapy |
MY128450A (en) | 2000-05-24 | 2007-02-28 | Upjohn Co | 1-(pyrrolidin-1-ylmethyl)-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives |
WO2001094312A2 (en) * | 2000-06-02 | 2001-12-13 | Sugen, Inc. | Indolinone derivatives as protein kinase/phosphatase inhibitors |
AR042586A1 (en) | 2001-02-15 | 2005-06-29 | Sugen Inc | 3- (4-AMIDOPIRROL-2-ILMETILIDEN) -2-INDOLINONE AS INHIBITORS OF PROTEIN KINASE; YOUR PHARMACEUTICAL COMPOSITIONS; A METHOD FOR THE MODULATION OF THE CATALYTIC ACTIVITY OF PROTEINQUINASE; A METHOD TO TREAT OR PREVENT AN AFFECTION RELATED TO PROTEINQUINASE |
US6599902B2 (en) | 2001-05-30 | 2003-07-29 | Sugen, Inc. | 5-aralkysufonyl-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives as kinase inhibitors |
AR038957A1 (en) * | 2001-08-15 | 2005-02-02 | Pharmacia Corp | COMBINATION THERAPY FOR CANCER TREATMENT |
BR0213185A (en) | 2001-10-10 | 2004-09-14 | Sugen Inc | 3- [4- (Substituted Heterocyclyl) -pyrrol-2-ylmethylidene] 2-indolinone derivatives as kinase inhibitors |
US20050119303A1 (en) * | 2002-03-05 | 2005-06-02 | Eisai Co., Ltd | Antitumor agent comprising combination of sulfonamide-containing heterocyclic compound with an angiogenesis inhibitor |
US20050107819A1 (en) * | 2003-11-14 | 2005-05-19 | Medtronic Vascular, Inc. | Catheter with a sectional guidewire shaft |
US8772269B2 (en) * | 2004-09-13 | 2014-07-08 | Eisai R&D Management Co., Ltd. | Use of sulfonamide-including compounds in combination with angiogenesis inhibitors |
WO2010149943A1 (en) * | 2009-06-25 | 2010-12-29 | Oncorel Ab | New compounds and medical use |
CN103274988B (en) * | 2013-06-20 | 2016-04-13 | 河北大学 | 3-(cyano group-p-nitrobenzoyl support group)-2-indolone derivatives and preparation method and use thereof |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3310891A1 (en) * | 1983-03-25 | 1984-09-27 | Boehringer Mannheim Gmbh, 6800 Mannheim | NEW INDOLINON (2) DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS AND INTERMEDIATE PRODUCTS |
JPH03213847A (en) * | 1990-01-18 | 1991-09-19 | Konica Corp | Silver halide photographic sensitive material |
GB9004483D0 (en) * | 1990-02-28 | 1990-04-25 | Erba Carlo Spa | New aryl-and heteroarylethenylene derivatives and process for their preparation |
-
1991
- 1991-07-12 GB GB919115160A patent/GB9115160D0/en active Pending
-
1992
- 1992-07-02 IL IL102383A patent/IL102383A/en not_active IP Right Cessation
- 1992-07-06 TW TW081105346A patent/TW202444B/zh active
- 1992-07-06 NZ NZ243454A patent/NZ243454A/en unknown
- 1992-07-08 MX MX9204008A patent/MX9204008A/en not_active IP Right Cessation
- 1992-07-10 DE DE69232093T patent/DE69232093T2/en not_active Expired - Fee Related
- 1992-07-10 JP JP50198193A patent/JP3188701B2/en not_active Expired - Fee Related
- 1992-07-10 AU AU22777/92A patent/AU656015B2/en not_active Ceased
- 1992-07-10 DK DK92914619T patent/DK0552329T3/en active
- 1992-07-10 US US07/987,280 patent/US5409949A/en not_active Expired - Lifetime
- 1992-07-10 HU HU9300723A patent/HUT67496A/en unknown
- 1992-07-10 EP EP92914619A patent/EP0552329B1/en not_active Expired - Lifetime
- 1992-07-10 ES ES92914619T patent/ES2165357T3/en not_active Expired - Lifetime
- 1992-07-10 EP EP19920111757 patent/EP0525472A3/en active Pending
- 1992-07-10 AT AT92914619T patent/ATE206420T1/en not_active IP Right Cessation
- 1992-07-10 RU RU9293004893A patent/RU2072989C1/en active
- 1992-07-10 WO PCT/EP1992/001569 patent/WO1993001182A1/en active IP Right Grant
- 1992-07-10 PT PT92914619T patent/PT552329E/en unknown
- 1992-07-10 IE IE225392A patent/IE922253A1/en not_active Application Discontinuation
- 1992-07-10 ZA ZA925169A patent/ZA925169B/en unknown
- 1992-07-10 CA CA002091058A patent/CA2091058C/en not_active Expired - Fee Related
-
1993
- 1993-03-10 FI FI931061A patent/FI931061A0/en not_active Application Discontinuation
- 1993-03-12 KR KR1019930700756A patent/KR930702337A/en not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
EP0525472A3 (en) | 1993-02-24 |
IL102383A (en) | 1997-09-30 |
HUT67496A (en) | 1995-04-28 |
GB9115160D0 (en) | 1991-08-28 |
EP0552329A1 (en) | 1993-07-28 |
JPH06501494A (en) | 1994-02-17 |
ES2165357T3 (en) | 2002-03-16 |
JP3188701B2 (en) | 2001-07-16 |
KR930702337A (en) | 1993-09-08 |
AU2277792A (en) | 1993-02-11 |
PT552329E (en) | 2002-02-28 |
US5409949A (en) | 1995-04-25 |
DE69232093D1 (en) | 2001-11-08 |
MX9204008A (en) | 1993-01-01 |
WO1993001182A1 (en) | 1993-01-21 |
DK0552329T3 (en) | 2001-11-12 |
NZ243454A (en) | 1995-02-24 |
DE69232093T2 (en) | 2002-05-16 |
IL102383A0 (en) | 1993-01-14 |
FI931061A (en) | 1993-03-10 |
EP0525472A2 (en) | 1993-02-03 |
EP0552329B1 (en) | 2001-10-04 |
TW202444B (en) | 1993-03-21 |
AU656015B2 (en) | 1995-01-19 |
RU2072989C1 (en) | 1997-02-10 |
IE922253A1 (en) | 1993-01-13 |
HU9300723D0 (en) | 1993-06-28 |
ZA925169B (en) | 1993-04-28 |
ATE206420T1 (en) | 2001-10-15 |
CA2091058C (en) | 2004-03-30 |
FI931061A0 (en) | 1993-03-10 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
MKLA | Lapsed |