ATE195734T1 - Aryliden-und heteroaryliden-oxindol derivate als tyrosin kinase inhibitoren - Google Patents

Aryliden-und heteroaryliden-oxindol derivate als tyrosin kinase inhibitoren

Info

Publication number
ATE195734T1
ATE195734T1 AT94918379T AT94918379T ATE195734T1 AT E195734 T1 ATE195734 T1 AT E195734T1 AT 94918379 T AT94918379 T AT 94918379T AT 94918379 T AT94918379 T AT 94918379T AT E195734 T1 ATE195734 T1 AT E195734T1
Authority
AT
Austria
Prior art keywords
tyrosine kinase
kinase inhibitors
heteroarylidene
arylidene
oxindole derivatives
Prior art date
Application number
AT94918379T
Other languages
English (en)
Inventor
Franco Buzzetti
Antonio Longo
Maria Gabriella Brasca
Fabrizio Orzi
Angelo Crugnola
Dario Ballinari
Mariangela Mariani
Original Assignee
Pharmacia & Upjohn Spa
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Pharmacia & Upjohn Spa filed Critical Pharmacia & Upjohn Spa
Application granted granted Critical
Publication of ATE195734T1 publication Critical patent/ATE195734T1/de

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • 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
    • 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
    • A61K31/40—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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/36—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/37—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by etherified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/41—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by carboxyl groups, other than cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C327/00—Thiocarboxylic acids
    • C07C327/38—Amides of thiocarboxylic acids
    • C07C327/40—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C327/42—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of a saturated carbon skeleton
    • 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
    • C07D209/18—Radicals substituted by 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D215/14—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
AT94918379T 1993-07-01 1994-05-26 Aryliden-und heteroaryliden-oxindol derivate als tyrosin kinase inhibitoren ATE195734T1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB939313638A GB9313638D0 (en) 1993-07-01 1993-07-01 Arylidene and heteroarylidene oxindole derivatives and process for their preparation
PCT/EP1994/001715 WO1995001349A1 (en) 1993-07-01 1994-05-26 Arylidene and heteroarylidene oxindole derivatives as tyrosine kinase inhibitors

Publications (1)

Publication Number Publication Date
ATE195734T1 true ATE195734T1 (de) 2000-09-15

Family

ID=10738142

Family Applications (2)

Application Number Title Priority Date Filing Date
AT99203366T ATE360013T1 (de) 1993-07-01 1994-05-26 Aryliden und heteroaryliden-oxindolderivate als tyrosin kinase inhibitoren
AT94918379T ATE195734T1 (de) 1993-07-01 1994-05-26 Aryliden-und heteroaryliden-oxindol derivate als tyrosin kinase inhibitoren

Family Applications Before (1)

Application Number Title Priority Date Filing Date
AT99203366T ATE360013T1 (de) 1993-07-01 1994-05-26 Aryliden und heteroaryliden-oxindolderivate als tyrosin kinase inhibitoren

Country Status (23)

Country Link
US (1) US5656654A (de)
EP (2) EP0658159B1 (de)
JP (1) JP3737826B2 (de)
KR (1) KR950702979A (de)
CN (1) CN1111454A (de)
AT (2) ATE360013T1 (de)
AU (1) AU679754B2 (de)
CA (1) CA2142472A1 (de)
DE (2) DE69434955T2 (de)
DK (1) DK0658159T3 (de)
ES (2) ES2300132T3 (de)
FI (1) FI950859A (de)
GB (1) GB9313638D0 (de)
GR (1) GR3034854T3 (de)
HU (1) HUT72047A (de)
IL (1) IL110131A0 (de)
MX (1) MX9404885A (de)
NZ (1) NZ267423A (de)
PL (1) PL307741A1 (de)
PT (1) PT658159E (de)
RU (1) RU95108244A (de)
WO (1) WO1995001349A1 (de)
ZA (1) ZA944730B (de)

Families Citing this family (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9501567D0 (en) * 1995-01-26 1995-03-15 Pharmacia Spa Hydrosoluble 3-arylidene-2-oxindole derivatives 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
US5977130A (en) * 1996-01-17 1999-11-02 Taiho Pharmeutical Co., Ltd. Intimal hypertrophy inhibitors
GB9610964D0 (en) * 1996-05-24 1996-07-31 Pharmacia & Upjohn Spa Substituted tetralylmethylen-oxindole analogues as tyrosine kinase inhibitors
GB9611797D0 (en) * 1996-06-06 1996-08-07 Pharmacia Spa Substituted quinolylmethylen-oxindole analogues as tyrosine kinase inhibitors
GB9613021D0 (en) * 1996-06-21 1996-08-28 Pharmacia Spa Bicyclic 4-aralkylaminopyrimidine derivatives as tyrosine kinase inhibitors
EP0929520B1 (de) * 1996-08-23 2005-11-02 Sugen, Inc. Kombinatorische bibliotheken von indolinone und verwandte produkte und verfahren zur behandlung von krankheiten
US5917028A (en) * 1996-10-29 1999-06-29 Incyte Pharmaceuticals, Inc. Human phosphoprotein
WO1998024432A2 (en) * 1996-12-05 1998-06-11 Sugen, Inc. Use of indolinone compounds as modulators of protein kinases
US6051593A (en) * 1997-06-20 2000-04-18 Sugen, Inc. 3-(cycloalkanoheteroarylidenyl)-2- indolinone protein tyrosine kinase inhibitors
GB9718913D0 (en) 1997-09-05 1997-11-12 Glaxo Group Ltd Substituted oxindole derivatives
US6133305A (en) 1997-09-26 2000-10-17 Sugen, Inc. 3-(substituted)-2-indolinones compounds and use thereof as inhibitors of protein kinase activity
US6531502B1 (en) 1998-01-21 2003-03-11 Sugen, Inc. 3-Methylidenyl-2-indolinone modulators of protein kinase
EP1060160A2 (de) 1998-02-27 2000-12-20 THE UNITED STATES GOVERNMENT as represented by THE DEPARTMENT OF HEALTH AND HUMAN SERVICES Disubstituirte lavendustin analogen und diese enthaltende pharmazeutische zusammensetzungen
DE19815020A1 (de) * 1998-04-03 1999-10-07 Boehringer Ingelheim Pharma Neue substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel
US6043254A (en) * 1998-04-03 2000-03-28 Boehringer Ingelheim Pharma Kg Indolinones having kinase-inhibiting activity
US6569868B2 (en) 1998-04-16 2003-05-27 Sugen, Inc. 2-indolinone derivatives as modulators of protein kinase activity
EP1117397A1 (de) * 1998-08-31 2001-07-25 Sugen, Inc. Geometrisch verhinderte 2-indolinonderivate als modulatoren der protein kinase aktivität
KR20010101266A (ko) 1998-12-17 2001-11-14 프리돌린 클라우스너, 롤란드 비. 보레르 Ｊｎｋ 단백질 키나제의 억제제로서의 4-아릴옥신돌
WO2000035908A1 (en) * 1998-12-17 2000-06-22 F. Hoffmann-La Roche Ag 4-alkenyl (and alkynyl) oxindoles as inhibitors of cyclin-dependent kinases, in particular cdk2
JP2002532503A (ja) 1998-12-17 2002-10-02 エフ．ホフマン−ラ ロシュ アーゲー プロテインキナーゼ阻害剤としての４，５−ピラジノオキシンドール
US6153634A (en) 1998-12-17 2000-11-28 Hoffmann-La Roche Inc. 4,5-azolo-oxindoles
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
GB9904933D0 (en) 1999-03-04 1999-04-28 Glaxo Group Ltd Compounds
EP1165513A1 (de) * 1999-03-24 2002-01-02 Sugen, Inc. Indolinon derivate als kinase inhibitoren
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
WO2001049287A1 (en) * 1999-12-30 2001-07-12 Sugen, Inc. 3-heteroarylidenyl-2-indolinone compounds for modulating protein kinase activity and for use in cancer chemotherapy
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
EP1294688A2 (de) 2000-06-02 2003-03-26 Sugen, Inc. Indolinon derivate als protein kinase/phosphatase inhibitoren
US6504034B2 (en) 2001-01-23 2003-01-07 Hoffmann-La Roche Inc. Naphthostyrils
WO2002096361A2 (en) 2001-05-30 2002-12-05 Sugen, Inc. 5-aralkylsulfonyl-3- (pyrrol-2-ylmethylidene)-2-indolinone derivatives as kinase inhibitors
US7314936B2 (en) * 2002-01-07 2008-01-01 Eisai Co., Ltd. Deazapurines and uses thereof
US7759383B2 (en) 2005-02-22 2010-07-20 The Regents Of The University Of Michigan Small molecule inhibitors of MDM2 and the uses thereof
CN102115469A (zh) * 2011-03-21 2011-07-06 浙江大学 吲哚啉-2-酮类衍生物的制备和用途
WO2014066840A1 (en) 2012-10-26 2014-05-01 Regents Of The University Of Minnesota Aurora kinase inhibitors
US10487054B2 (en) 2017-04-21 2019-11-26 Regents Of The University Of Minnesota Therapeutic compounds

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9000950D0 (en) * 1990-01-16 1990-03-14 Erba Carlo Spa New arylvinylamide derivatives and process for their preparation
GB9000939D0 (en) * 1990-01-16 1990-03-14 Erba Carlo Spa Improvement in the total synthesis of erbstatin analogs
GB9004483D0 (en) * 1990-02-28 1990-04-25 Erba Carlo Spa New aryl-and heteroarylethenylene derivatives and process for their preparation
WO1992007830A2 (en) * 1990-10-29 1992-05-14 Pfizer Inc. Oxindole peptide antagonists
GB9115160D0 (en) * 1991-07-12 1991-08-28 Erba Carlo Spa Methylen-oxindole derivatives and process for their preparation
EP0549348A1 (de) * 1991-12-24 1993-06-30 PHARMACIA S.p.A. Arylidene-heterocyclische Derivate, Verfahren zu ihrer Herstellung und ihre Anwendung als Tyrisine-Kinase Inhibitoren

Also Published As

Publication number Publication date
PL307741A1 (en) 1995-06-12
ATE360013T1 (de) 2007-05-15
WO1995001349A1 (en) 1995-01-12
FI950859A0 (fi) 1995-02-24
AU679754B2 (en) 1997-07-10
DE69434955T2 (de) 2008-01-17
ES2300132T3 (es) 2008-06-01
EP0658159B1 (de) 2000-08-23
MX9404885A (es) 1995-01-31
EP0658159A1 (de) 1995-06-21
JPH08500847A (ja) 1996-01-30
EP0987263A2 (de) 2000-03-22
CN1111454A (zh) 1995-11-08
HU9500954D0 (en) 1995-05-29
IL110131A0 (en) 1994-10-07
DK0658159T3 (da) 2000-12-18
DE69434955D1 (de) 2007-05-31
ES2152317T3 (es) 2001-02-01
DE69425637T2 (de) 2001-05-03
EP0987263A3 (de) 2003-10-15
NZ267423A (en) 1996-03-26
US5656654A (en) 1997-08-12
KR950702979A (ko) 1995-08-23
CA2142472A1 (en) 1995-01-12
AU6971994A (en) 1995-01-24
EP0987263B1 (de) 2007-04-18
ZA944730B (en) 1995-07-13
RU95108244A (ru) 1997-03-20
FI950859A (fi) 1995-02-24
HUT72047A (en) 1996-03-28
GB9313638D0 (en) 1993-08-18
PT658159E (pt) 2001-01-31
GR3034854T3 (en) 2001-02-28
DE69425637D1 (de) 2000-09-28
JP3737826B2 (ja) 2006-01-25

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