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EP1042329A1 - Farnesyltransferase inhibitoren, verfahren zu ihrer herstellung, diese enthaltende pharmazeutische zubereitungen und ihre verwendung als arzneimittel - Google Patents

Farnesyltransferase inhibitoren, verfahren zu ihrer herstellung, diese enthaltende pharmazeutische zubereitungen und ihre verwendung als arzneimittel

Info

Publication number
EP1042329A1
EP1042329A1 EP98962528A EP98962528A EP1042329A1 EP 1042329 A1 EP1042329 A1 EP 1042329A1 EP 98962528 A EP98962528 A EP 98962528A EP 98962528 A EP98962528 A EP 98962528A EP 1042329 A1 EP1042329 A1 EP 1042329A1
Authority
EP
European Patent Office
Prior art keywords
general formula
radical
compounds
alkyl
het
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.)
Withdrawn
Application number
EP98962528A
Other languages
English (en)
French (fr)
Inventor
Norbert Dereu
Patrick Mailliet
Fabienne Sounigo-Thompson
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.)
Aventis Pharma SA
Original Assignee
Aventis Pharma SA
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
Priority claimed from FR9716335A external-priority patent/FR2772764B1/fr
Application filed by Aventis Pharma SA filed Critical Aventis Pharma SA
Publication of EP1042329A1 publication Critical patent/EP1042329A1/de
Withdrawn legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/08Drugs for disorders of the urinary system of the prostate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/06Antipsoriatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44Iso-indoles; Hydrogenated iso-indoles
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08Bridged systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D495/00Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/08Bridged systems

Definitions

  • the present invention relates to new derivatives of general formula (I)
  • the farnesyl transferase protein is an enzyme which catalyzes the transfer of the farnesyl group of farnesyl pyrophosphate (FPP) to the terminal cysteine residue of the tetrapeptide CAAX sequence of a certain number of proteins and in particular of the protein p21Ras, expressing the ras oncogene. .
  • the ras oncogene (H-, N- or K-ras) is known to play a key role in cell signaling pathways and cell division processes.
  • the present invention relates to new compounds of general formula I
  • one of the symbols Ri or R 2 represents a hydrogen atom and the other of the symbols represents an alkoxy radical such as methoxy, and more advantageously fixed in the ortho position of the phenyl ring.
  • R represents a carboxy radical, or a -COOMe radical, or also a -CON (R 5 ) (R6) radical for which R 5 represents a hydrogen atom, and Ré represents an alkyl radical such as methyl substituted by the phenyl radical or 3- or 4-pyridyl; one of the symbols Ri or R 2 represents a hydrogen atom and the other of the symbols represents an alkoxy radical such as methoxy, and more advantageously fixed in the ortho position of the phenyl ring, R 3 represents a hydrogen atom,
  • R ' identical or different, and R ", identical or different, represent alkyl radicals containing 1 to 10 carbon atoms
  • G represents an electron-attracting group
  • n represents an integer between 3 and 13 inclusive , whose porosity is close to 100 A
  • the anhydride of N-tert-butoxycarbonyl-11-amino-decanoic acid can be prepared in the following manner:

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Dermatology (AREA)
  • Endocrinology (AREA)
  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pulmonology (AREA)
  • Hematology (AREA)
  • Reproductive Health (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Indole Compounds (AREA)
EP98962528A 1997-12-23 1998-12-21 Farnesyltransferase inhibitoren, verfahren zu ihrer herstellung, diese enthaltende pharmazeutische zubereitungen und ihre verwendung als arzneimittel Withdrawn EP1042329A1 (de)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
FR9716335A FR2772764B1 (fr) 1997-12-23 1997-12-23 Nouveaux inhibiteurs de farnesyle transferase, leur preparation, les compositions pharmaceutiques qui les contiennent et leur utilisation pour la preparation de medicaments
FR9716335 1997-12-23
US7380098P 1998-02-05 1998-02-05
US73800P 1998-02-05
PCT/FR1998/002804 WO1999033834A1 (fr) 1997-12-23 1998-12-21 Nouveaux inhibiteurs de farnesyle transferase, leur preparation, les compositions pharmaceutiques qui les contiennent et leur utilisation pour la preparation de medicaments

Publications (1)

Publication Number Publication Date
EP1042329A1 true EP1042329A1 (de) 2000-10-11

Family

ID=26234014

Family Applications (1)

Application Number Title Priority Date Filing Date
EP98962528A Withdrawn EP1042329A1 (de) 1997-12-23 1998-12-21 Farnesyltransferase inhibitoren, verfahren zu ihrer herstellung, diese enthaltende pharmazeutische zubereitungen und ihre verwendung als arzneimittel

Country Status (5)

Country Link
EP (1) EP1042329A1 (de)
JP (1) JP2001527078A (de)
AU (1) AU1767599A (de)
CA (1) CA2315144A1 (de)
WO (1) WO1999033834A1 (de)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2787327B1 (fr) * 1998-12-21 2003-01-17 Aventis Pharma Sa Compositions contenant des inhibiteurs de farnesyle transferase
FR2796641B1 (fr) * 1999-07-22 2001-09-21 Aventis Pharma Sa Nouveau procede de preparation de composes benzoperhydroisoindole
CA2559285A1 (en) * 2004-03-18 2005-09-29 Brigham And Women's Hospital, Inc. Methods for the treatment of synucleinopathies
JP2007538004A (ja) * 2004-03-18 2007-12-27 ザ ブライハム アンド ウイメンズ ホスピタル, インコーポレイテッド シヌクレイノパチーを治療する方法
WO2005089496A2 (en) * 2004-03-18 2005-09-29 The Brigham And Women's Hospital, Inc. Methods for the treatment of synucleinopathies
EP1656931A1 (de) * 2004-11-15 2006-05-17 Exonhit Therapeutics SA Verbindungen, die die Protein Prenylierung hemmt, für die Bahandlung von Parkinsons Krankheit

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2736641B1 (fr) * 1995-07-10 1997-08-22 Rhone Poulenc Rorer Sa Nouveaux inhibiteurs de farnesyl transferase, leur preparation et les compositions pharmaceutiques qui les contiennent

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9933834A1 *

Also Published As

Publication number Publication date
CA2315144A1 (fr) 1999-07-08
JP2001527078A (ja) 2001-12-25
WO1999033834A1 (fr) 1999-07-08
AU1767599A (en) 1999-07-19

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