ES2152317T3 - Derivados de arilideno y de heteroarilideno oxiindol utilizados como inhibidores de la tirosina quinasa. - Google Patents

Derivados de arilideno y de heteroarilideno oxiindol utilizados como inhibidores de la tirosina quinasa.

Info

Publication number
ES2152317T3
ES2152317T3 ES94918379T ES94918379T ES2152317T3 ES 2152317 T3 ES2152317 T3 ES 2152317T3 ES 94918379 T ES94918379 T ES 94918379T ES 94918379 T ES94918379 T ES 94918379T ES 2152317 T3 ES2152317 T3 ES 2152317T3
Authority
ES
Spain
Prior art keywords
hydrogen
inhibitors
rent
derivatives
oxiindol
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 - Lifetime
Application number
ES94918379T
Other languages
English (en)
Inventor
Franco Buzzetti
Antonio Longo
Maria Gabriella Brasca
Fabrizio Orzi
Angelo Crugnola
Dario Ballinari
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pfizer Italia SRL
Original Assignee
Pharmacia and 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 and Upjohn SpA filed Critical Pharmacia and Upjohn SpA
Application granted granted Critical
Publication of ES2152317T3 publication Critical patent/ES2152317T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Indole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Quinoline Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

DERIVADOS DE OXINDOLA DE ARILIDENO Y HETEROARILIDENO, DE FORMULA (I), EN LA QUE, CONFORME A DISPOSICIONES, Y ES UN SISTEMA DE ANILLO BICICLICO SELECCIONADO ENTRE NAFTALENO, TETRALIN, QUINOLINA E ISOQUINOLINA; R ES HIDROGENO O UN GRUPO OXO (=O), CUANDO Y ES TETRALINA; O R ES HIDROGENO CUANDO Y ES NAFTALENO, QUINOLINA O ISOQUINOLINA; CADA UNO DE R1 Y R2 INDEPENDIENTEMENTE ES HIDROGENO, C1 - C6 ALQUILO, O C2 - C6 ALCANOLILO; M ES CERO, 1 O 2; N ES CERO, 1, 2 O 3; CADA UNO DE R3 Y R4 INDEPENDIENTEMENTE ES HIDROGENO, HALOGENO, CIANO, C1 - C6 ALQUILO, CARBOXI, NITRO O - NR6R7, EN EL QUE CADA UNO DE R6 Y R7 INDEPENDIENTEMENTE ES HIDROGENO O C1 - C6 ALQUILO; R5 ES HIDROGENO O C1 - C6 ALQUILO; Y SUS SALES FARMACEUTICAMENTE ACEPTABLES, QUE SON UTILES COMO INHIBIDORES DE QUINASA DE TIROSINA.
ES94918379T 1993-07-01 1994-05-26 Derivados de arilideno y de heteroarilideno oxiindol utilizados como inhibidores de la tirosina quinasa. Expired - Lifetime ES2152317T3 (es)

Applications Claiming Priority (1)

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

Publications (1)

Publication Number Publication Date
ES2152317T3 true ES2152317T3 (es) 2001-02-01

Family

ID=10738142

Family Applications (2)

Application Number Title Priority Date Filing Date
ES94918379T Expired - Lifetime ES2152317T3 (es) 1993-07-01 1994-05-26 Derivados de arilideno y de heteroarilideno oxiindol utilizados como inhibidores de la tirosina quinasa.
ES99203366T Expired - Lifetime ES2300132T3 (es) 1993-07-01 1994-05-26 Derivados de arileno y heteroarilideno-oxindoles como inhibidores de la tirosina quinasa.

Family Applications After (1)

Application Number Title Priority Date Filing Date
ES99203366T Expired - Lifetime ES2300132T3 (es) 1993-07-01 1994-05-26 Derivados de arileno y heteroarilideno-oxindoles como inhibidores de la tirosina quinasa.

Country Status (23)

Country Link
US (1) US5656654A (es)
EP (2) EP0658159B1 (es)
JP (1) JP3737826B2 (es)
KR (1) KR950702979A (es)
CN (1) CN1111454A (es)
AT (2) ATE360013T1 (es)
AU (1) AU679754B2 (es)
CA (1) CA2142472A1 (es)
DE (2) DE69434955T2 (es)
DK (1) DK0658159T3 (es)
ES (2) ES2152317T3 (es)
FI (1) FI950859A0 (es)
GB (1) GB9313638D0 (es)
GR (1) GR3034854T3 (es)
HU (1) HUT72047A (es)
IL (1) IL110131A0 (es)
MX (1) MX9404885A (es)
NZ (1) NZ267423A (es)
PL (1) PL307741A1 (es)
PT (1) PT658159E (es)
RU (1) RU95108244A (es)
WO (1) WO1995001349A1 (es)
ZA (1) ZA944730B (es)

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GB9501567D0 (en) * 1995-01-26 1995-03-15 Pharmacia Spa Hydrosoluble 3-arylidene-2-oxindole derivatives as tyrosine kinase inhibitors
US6906093B2 (en) 1995-06-07 2005-06-14 Sugen, Inc. Indolinone combinatorial libraries and related products and methods for the treatment of disease
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
ATE243034T1 (de) * 1996-01-17 2003-07-15 Taiho Pharmaceutical Co Ltd Intimale verdickungsinhibitoren
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
WO1998007695A1 (en) * 1996-08-23 1998-02-26 Sugen, Inc. Indolinone combinatorial libraries and related products and methods for the treatment of disease
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
WO1999043636A2 (en) 1998-02-27 1999-09-02 The United States Of America As Represented By Thesecretary Of The Department Of Health And Human Services Disubstituted lavendustin a analogs and pharmaceutical compositions comprising the analogs
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
JP2002523455A (ja) 1998-08-31 2002-07-30 スージェン・インコーポレーテッド 蛋白質キナーゼ活性の調節剤としての幾何学的に制限された２−インドリノン誘導体
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US10487054B2 (en) 2017-04-21 2019-11-26 Regents Of The University Of Minnesota Therapeutic compounds

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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 (en) * 1991-12-24 1993-06-30 PHARMACIA S.p.A. Arylidene-heterocyclic derivatives, process for their preparation and their use as tyrisine kinase inhibitors

Also Published As

Publication number Publication date
AU6971994A (en) 1995-01-24
HUT72047A (en) 1996-03-28
EP0987263A3 (en) 2003-10-15
WO1995001349A1 (en) 1995-01-12
GR3034854T3 (en) 2001-02-28
MX9404885A (es) 1995-01-31
PT658159E (pt) 2001-01-31
AU679754B2 (en) 1997-07-10
KR950702979A (ko) 1995-08-23
FI950859A7 (fi) 1995-02-24
EP0658159A1 (en) 1995-06-21
JP3737826B2 (ja) 2006-01-25
DK0658159T3 (da) 2000-12-18
FI950859A0 (fi) 1995-02-24
PL307741A1 (en) 1995-06-12
CN1111454A (zh) 1995-11-08
DE69425637T2 (de) 2001-05-03
EP0658159B1 (en) 2000-08-23
RU95108244A (ru) 1997-03-20
CA2142472A1 (en) 1995-01-12
DE69425637D1 (de) 2000-09-28
ATE195734T1 (de) 2000-09-15
EP0987263B1 (en) 2007-04-18
GB9313638D0 (en) 1993-08-18
IL110131A0 (en) 1994-10-07
EP0987263A2 (en) 2000-03-22
HU9500954D0 (en) 1995-05-29
DE69434955T2 (de) 2008-01-17
ZA944730B (en) 1995-07-13
US5656654A (en) 1997-08-12
ATE360013T1 (de) 2007-05-15
ES2300132T3 (es) 2008-06-01
JPH08500847A (ja) 1996-01-30
DE69434955D1 (de) 2007-05-31
NZ267423A (en) 1996-03-26

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