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WO1996010034A3 - Inhibiteurs de la transferase de proteines farnesylees exempts de thiol - Google Patents

Inhibiteurs de la transferase de proteines farnesylees exempts de thiol Download PDF

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Publication number
WO1996010034A3
WO1996010034A3 PCT/US1995/012224 US9512224W WO9610034A3 WO 1996010034 A3 WO1996010034 A3 WO 1996010034A3 US 9512224 W US9512224 W US 9512224W WO 9610034 A3 WO9610034 A3 WO 9610034A3
Authority
WO
WIPO (PCT)
Prior art keywords
thiol
ras
caax
inhibitors
analogs
Prior art date
Application number
PCT/US1995/012224
Other languages
English (en)
Other versions
WO1996010034A2 (fr
Inventor
Neville J Anthony
S Jane Desolms
Robert P Gomez
Samuel L Graham
John H Hutchinson
Gerald E Stokker
Original Assignee
Merck & Co Inc
Neville J Anthony
S Jane Desolms
Robert P Gomez
Samuel L Graham
John H Hutchinson
Gerald E Stokker
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 US08/526,244 external-priority patent/US5652257A/en
Application filed by Merck & Co Inc, Neville J Anthony, S Jane Desolms, Robert P Gomez, Samuel L Graham, John H Hutchinson, Gerald E Stokker filed Critical Merck & Co Inc
Priority to EP95935104A priority Critical patent/EP0783517A2/fr
Priority to CA 2201348 priority patent/CA2201348A1/fr
Priority to AU37248/95A priority patent/AU700175B2/en
Priority to JP8511933A priority patent/JPH10508005A/ja
Publication of WO1996010034A2 publication Critical patent/WO1996010034A2/fr
Publication of WO1996010034A3 publication Critical patent/WO1996010034A3/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
    • 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
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/0205—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof
    • 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
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Animal Behavior & Ethology (AREA)
  • Molecular Biology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention porte sur des analogues du motif CAAX de la protéine Ras modifiés in vivo par farnésylation. Lesdits analogues, qui inhibent la farnésylation de la Ras, diffèrent par ailleurs de ceux précédemment décrits comme inhibiteurs de la Ras farnésyle transférase en ce qu'ils ne présentent pas de fraction thiol. Cette absence de thiol offre des avantages uniques en matière d'amélioration du comportement pharmacocinétique chez les animaux, de prévention des réactions chimiques liées aux thiols telles que la rapidité de l'auto-oxydation, la formation de bisulfures avec les thiols endogènes et une toxicité systémique réduite. L'invention porte également sur des compositions chimiothérapeutiques contenant les susdits inhibiteurs et sur leur procédé d'obtention.
PCT/US1995/012224 1994-09-29 1995-09-26 Inhibiteurs de la transferase de proteines farnesylees exempts de thiol WO1996010034A2 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP95935104A EP0783517A2 (fr) 1994-09-29 1995-09-26 Inhibiteurs de la transferase de proteines farnesylees exempts de thiol
CA 2201348 CA2201348A1 (fr) 1994-09-29 1995-09-26 Inhibiteurs de la transferase de proteines farnesylees exempts de thiol
AU37248/95A AU700175B2 (en) 1994-09-29 1995-09-26 Thiol-free inhibitors of farnesyl-protein transferase
JP8511933A JPH10508005A (ja) 1994-09-29 1995-09-26 チオールを有しないファルネシル−タンパク質トランスフェラーゼ阻害剤

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US526,244 1990-05-18
US31497494A 1994-09-29 1994-09-29
US314,974 1994-09-29
US08/526,244 US5652257A (en) 1994-09-29 1995-09-21 Heterocycle-containing inhibitors of farnesyl-protein transferase

Publications (2)

Publication Number Publication Date
WO1996010034A2 WO1996010034A2 (fr) 1996-04-04
WO1996010034A3 true WO1996010034A3 (fr) 1996-05-09

Family

ID=26979651

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1995/012224 WO1996010034A2 (fr) 1994-09-29 1995-09-26 Inhibiteurs de la transferase de proteines farnesylees exempts de thiol

Country Status (5)

Country Link
EP (1) EP0783517A2 (fr)
JP (1) JPH10508005A (fr)
AU (1) AU700175B2 (fr)
IL (1) IL115471A0 (fr)
WO (1) WO1996010034A2 (fr)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0880320A4 (fr) * 1996-01-30 1999-06-16 Merck & Co Inc Inhibiteurs de la farnesyl-proteine transferase
AU716153B2 (en) * 1996-04-03 2000-02-17 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
JP2000507579A (ja) * 1996-04-03 2000-06-20 メルク エンド カンパニー インコーポレーテッド ファルネシル―タンパク質トランスフェラーゼ阻害剤
CA2250460A1 (fr) * 1996-04-03 1997-10-09 John H. Hutchinson Inhibiteurs de transferase de farnesyl-proteine
JP2000507597A (ja) * 1996-04-03 2000-06-20 メルク エンド カンパニー インコーポレーテッド ファルネシルタンパク質トランスフェラーゼ阻害剤
EP0944388A4 (fr) * 1996-04-03 2001-08-16 Merck & Co Inc Inhibiteurs de la farnesyl-proteine transferase
US5932590A (en) * 1996-12-05 1999-08-03 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
AU2003215272B2 (en) 2002-02-14 2008-04-03 The Board Of Trustees Of The Leland Stanford Junior University Enzyme treatment of foodstuffs for celiac sprue
US8143210B2 (en) 2002-02-14 2012-03-27 The Board Of Trustees Of The Leland Stanford Junior University Enzyme treatment of foodstuffs for celiac sprue
AU2003234634A1 (en) * 2002-05-14 2003-12-02 Felix Hausch Drug therapy for celiac sprue
AU2003294473A1 (en) 2002-11-20 2004-06-15 The Board Of Trustees Of The Leland Stanford Junior University Diagnostic method for celiac sprue
US7579313B2 (en) 2003-11-18 2009-08-25 The Board Of Trustees Of The Leland Stanford Junior University Transglutaminase inhibitors and methods of use thereof
BRPI0808987A2 (pt) 2007-03-16 2014-09-09 Univ Leland Stanford Junior Terapia combinatória de enzima para digestão de glúten dietético

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991016340A1 (fr) * 1990-04-18 1991-10-31 Board Of Regents, The University Of Texas System Procedes et compositions servant a l'identification, a la caracterisation et a l'inhibition de la transferase de proteine farnesyle
WO1995009000A1 (fr) * 1993-09-30 1995-04-06 Merck & Co., Inc. Inhibiteurs de farnesyle-proteine transferase
WO1995012612A1 (fr) * 1993-11-05 1995-05-11 Warner-Lambert Company Inhibiteurs di- et tripeptidiques substitues de l'enzyme proteine:la farnesyle transferase

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991016340A1 (fr) * 1990-04-18 1991-10-31 Board Of Regents, The University Of Texas System Procedes et compositions servant a l'identification, a la caracterisation et a l'inhibition de la transferase de proteine farnesyle
WO1995009000A1 (fr) * 1993-09-30 1995-04-06 Merck & Co., Inc. Inhibiteurs de farnesyle-proteine transferase
WO1995012612A1 (fr) * 1993-11-05 1995-05-11 Warner-Lambert Company Inhibiteurs di- et tripeptidiques substitues de l'enzyme proteine:la farnesyle transferase

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
JAMES, G.L.ET AL.: "Benzodiazepine peptidomimetics: potent inhibitors of Ras farnesylation in animal cells", SCIENCE, vol. 260, 25 June 1993 (1993-06-25), pages 1937 - 1942 *

Also Published As

Publication number Publication date
AU700175B2 (en) 1998-12-24
JPH10508005A (ja) 1998-08-04
AU3724895A (en) 1996-04-19
WO1996010034A2 (fr) 1996-04-04
IL115471A0 (en) 1995-12-31
EP0783517A2 (fr) 1997-07-16

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