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WO1996034010A3 - Inhibiteurs de la farnesyle transferase - Google Patents

Inhibiteurs de la farnesyle transferase Download PDF

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Publication number
WO1996034010A3
WO1996034010A3 PCT/US1996/003975 US9603975W WO9634010A3 WO 1996034010 A3 WO1996034010 A3 WO 1996034010A3 US 9603975 W US9603975 W US 9603975W WO 9634010 A3 WO9634010 A3 WO 9634010A3
Authority
WO
WIPO (PCT)
Prior art keywords
farnesyl
ca1a2x
inhibitors
thiol
analogs
Prior art date
Application number
PCT/US1996/003975
Other languages
English (en)
Other versions
WO1996034010A2 (fr
Inventor
S Jane Desolms
Original Assignee
Merck & Co Inc
S Jane Desolms
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 Merck & Co Inc, S Jane Desolms filed Critical Merck & Co Inc
Priority to AU68950/96A priority Critical patent/AU708620B2/en
Priority to EP96929648A priority patent/EP0837875A4/fr
Priority to JP8528692A priority patent/JPH11502822A/ja
Publication of WO1996034010A2 publication Critical patent/WO1996034010A2/fr
Publication of WO1996034010A3 publication Critical patent/WO1996034010A3/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Communicable Diseases (AREA)
  • Biophysics (AREA)
  • Oncology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Biochemistry (AREA)
  • Virology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Urology & Nephrology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention comporte des analogues du motif structural CA1A2X de la protéine Ras, laquelle est modifiée par farnésylation in vivo. Ces analogues de CA1A2X inhibent la farnésyle transférase ainsi que la farnésylation de certaines protéines. En outre, ces analogues de CA1A2X diffèrent de ceux précédemment décrits en tant qu'inhibiteurs de la farnésyle transférase, en ce qu'ils sont dépourvus d'une fraction thiol. Cette absence de fraction thiol offre des avantages uniques, en termes d'un meilleur comportement pharmacocinétique de ces analogues chez les animaux, d'une prévention de réactions chimiques dépendant des thiols, telles qu'une autoxydation rapide et une formation de disulfure avec les thiols endogènes, et d'une toxicité systématique réduite. Les composés selon l'invention comprennent également une fraction amine cyclique en position A2 du motif structural. On décrit encore dans cette invention des compositions chimiothérapeutiques contenant ces inhibiteurs de farnésyle transférase, ainsi que des procédés de production de ceux-ci.
PCT/US1996/003975 1995-03-29 1996-03-25 Inhibiteurs de la farnesyle transferase WO1996034010A2 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU68950/96A AU708620B2 (en) 1995-03-29 1996-03-25 Inhibitors of farnesyl-protein transferase
EP96929648A EP0837875A4 (fr) 1995-03-29 1996-03-25 Inhibiteurs de la farnesyle transferase
JP8528692A JPH11502822A (ja) 1995-03-29 1996-03-25 ファルネシル−タンパク質トランスフェラーゼ阻害剤

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US41282895A 1995-03-29 1995-03-29
US41262695A 1995-03-29 1995-03-29
US08/412,828 1995-03-29
US08/412,626 1995-03-29
US441995P 1995-09-27 1995-09-27
US60/004,419 1995-09-27

Publications (2)

Publication Number Publication Date
WO1996034010A2 WO1996034010A2 (fr) 1996-10-31
WO1996034010A3 true WO1996034010A3 (fr) 1996-12-12

Family

ID=56289685

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/003975 WO1996034010A2 (fr) 1995-03-29 1996-03-25 Inhibiteurs de la farnesyle transferase

Country Status (1)

Country Link
WO (1) WO1996034010A2 (fr)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5703241A (en) * 1995-10-16 1997-12-30 Merck & Co., Inc. Inhibitor of farnesyl-protein transferase
WO1997036891A1 (fr) * 1996-04-03 1997-10-09 Merk & Co., Inc. Inhibiteurs de la farnesyl-proteine transferase
IN2014CN02806A (fr) 2011-10-14 2015-07-03 Bristol Myers Squibb Co
DK2766346T3 (en) 2011-10-14 2017-07-03 Bristol Myers Squibb Co SUBSTITUTED TETRAHYDROISOQUINOL COMPOUNDS AS FACTOR XIA INHIBITORS
US9079929B2 (en) 2011-10-14 2015-07-14 Bristol-Myers Squibb Company Substituted tetrahydroisoquinoline compounds as factor XIa inhibitors
EP2906551B1 (fr) 2012-10-12 2018-02-28 Bristol-Myers Squibb Company Formes cristallines d'un inhibiteur de facteur xia
EP2906541B1 (fr) 2012-10-12 2017-11-22 Bristol-Myers Squibb Company Composés de tetrahydroisoquinoline substitués par guanidine et amine en tant qu'inhibiteurs de factor xia
EP2906552B1 (fr) 2012-10-12 2017-11-22 Bristol-Myers Squibb Company Composés de tetrahydroisoquinoline substitués par guanidine en tant qu'inhibiteurs de factor xia
EP2978751B1 (fr) 2013-03-25 2018-12-05 Bristol-Myers Squibb Company Tétrahydroisoquinolines comprenant des azoles substitués en tant qu'inhibiteurs du facteur xia
NO2760821T3 (fr) 2014-01-31 2018-03-10
MX377545B (es) 2014-01-31 2025-03-10 Bristol Myers Squibb Co Macrociclos con grupos p2' heterocíclicos como inhibidores del factor xia.
CN107074821B (zh) 2014-09-04 2020-05-22 百时美施贵宝公司 为fxia抑制剂的二酰胺大环化合物
US9453018B2 (en) 2014-10-01 2016-09-27 Bristol-Myers Squibb Company Pyrimidinones as factor XIa inhibitors

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5238922A (en) * 1991-09-30 1993-08-24 Merck & Co., Inc. Inhibitors of farnesyl protein transferase
US5326773A (en) * 1992-10-29 1994-07-05 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5340828A (en) * 1991-09-30 1994-08-23 Merck & Co., Inc. Inhibitors of farnesyl protein transferase
US5504212A (en) * 1992-10-29 1996-04-02 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5238922A (en) * 1991-09-30 1993-08-24 Merck & Co., Inc. Inhibitors of farnesyl protein transferase
US5340828A (en) * 1991-09-30 1994-08-23 Merck & Co., Inc. Inhibitors of farnesyl protein transferase
US5326773A (en) * 1992-10-29 1994-07-05 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5504212A (en) * 1992-10-29 1996-04-02 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CANCER RESEARCH, September 1989, Volume 49, BOS, "Ras Oncogenes in Human Cancer: A Review", pages 4682-4689. *
NATURAL MEDICINE, August 1995, Vol. 1, No. 8, KOHL et al., "Inhibition of Farnesyltransferase Induces Regression of Mammary and Salivary Carcinomas in Ras Transgenic Mice", pages 792-797. *
See also references of EP0837875A4 *

Also Published As

Publication number Publication date
WO1996034010A2 (fr) 1996-10-31

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