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

Info

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 CA 2201348 priority Critical patent/CA2201348A1/fr
Priority to JP8511933A priority patent/JPH10508005A/ja
Priority to AU37248/95A priority patent/AU700175B2/en
Priority to EP95935104A priority patent/EP0783517A2/fr
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)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (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)

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
CA 2201348 CA2201348A1 (fr) 1994-09-29 1995-09-26 Inhibiteurs de la transferase de proteines farnesylees exempts de thiol
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
AU37248/95A AU700175B2 (en) 1994-09-29 1995-09-26 Thiol-free inhibitors of farnesyl-protein transferase
EP95935104A EP0783517A2 (fr) 1994-09-29 1995-09-26 Inhibiteurs de la transferase de proteines farnesylees exempts de thiol

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
CA2243507A1 (fr) * 1996-01-30 1997-08-07 Christopher J. Dinsmore Inhibiteurs de la farnesyl-proteine transferase
WO1997036877A1 (fr) * 1996-04-03 1997-10-09 Merck & Co., Inc. Inhibiteurs de transferase de farnesyl-proteine
CA2249601A1 (fr) * 1996-04-03 1997-10-23 Thorsten E. Fisher Inhibiteurs de la farnesyl-proteine transferase
WO1997036891A1 (fr) * 1996-04-03 1997-10-09 Merk & Co., Inc. Inhibiteurs de la farnesyl-proteine transferase
AU707139B2 (en) * 1996-04-03 1999-07-01 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
AU716153B2 (en) * 1996-04-03 2000-02-17 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5932590A (en) * 1996-12-05 1999-08-03 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
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
DK1572127T4 (da) 2002-02-14 2014-11-24 Univ Leland Stanford Junior Enzymbehandling af fødevarer til cøliaki
WO2004045392A2 (fr) 2002-11-20 2004-06-03 The Board Of Trustees Of The Leland Stanford Junior University Procede de diagnostic de la maladie coeliaque
WO2003096984A2 (fr) * 2002-05-14 2003-11-27 The Board Of Trustees Of The Leland Stanford Junior University Pharmacotherapie contre la maladie coeliaque
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
NZ580425A (en) 2007-03-16 2011-12-22 Univ Leland Stanford Junior Combination enzyme therapy for digestion of dietary gluten

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

Similar Documents

Publication Publication Date Title
WO1996010034A3 (fr) Inhibiteurs de la transferase de proteines farnesylees exempts de thiol
WO1996034010A3 (fr) Inhibiteurs de la farnesyle transferase
AU5455394A (en) Inhibitors of farnesyl-protein transferase
PL308554A1 (en) Inhibitors of farnesil-protein transferase
BG102738A (en) Inhibitors of farnesyl-protein transferase
WO1994026723A3 (fr) INHIBITEURS DE LA ras FARNESYL-TRANSFERASE
IL120266A (en) Use of estrogen antagonists and estrogen agonists in the preparation of medicaments for inhibiting pathological conditions
SI1246809T1 (en) 5-aryl-1h-1,2,4-triazole compounds as inhibitors of cyclooxygenase-2 and pharmaceutical compositions containing them
DE3233697C2 (fr)
WO2000034437A3 (fr) Inhibiteurs de prenyl-proteine transferase
AU6024086A (en) Nitrogen containing heterocyclic oxo and thio compounds useful as pesticides
WO1996031525A3 (fr) Inhibiteurs de la farnesyl-proteine transferase
AU4696199A (en) 5-ht1f agonists
FR2572399B1 (fr) Nouveaux derives de l'adamantanamine, leurs procedes de preparation et medicaments les contenant
AU1634288A (en) Cyclic anticoagulant peptides
WO1996023771A3 (fr) Inhibiteurs de l'agregation plaquettaire
GR3034615T3 (en) Aminophenylalanine derivatives, process for their production, their use and agents containing them as anti-coagulants.
WO2001076390A3 (fr) Aromatisation d'un aliment par incorporation d'une quantite effective d'au moins un compose de formule r1-s-r2 dans laquelle r1 et r2 representent un atome ou un groupe specifique
WO2000000490A3 (fr) Agonistes de 5-ht¿1f?
NZ214357A (en) Pharmaceutical composition which includes at least one immunotoxin and at least one mannose-containing polymer
CY2230B1 (en) Stable pharmaceutical compositions containing hybrid alpha-interferon
Breslin et al. Inhibitors of farnesyl-protein transferase
AU2717100A (en) Prenyl transferase inhibitors
WO2000034239A3 (fr) Inhibiteurs de prenyl-proteine transferase
CA2154871A1 (fr) Inhibiteurs de farnesyl-proteine-transferase, agents anti-cancer

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AM AU BB BG BR BY CA CN CZ EE FI GE HU IS JP KG KR KZ LK LR LT LV MD MG MK MN MX NO NZ PL RO RU SG SI SK TJ TM TT UA UG US US UZ

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): KE MW SD SZ UG AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 1995935104

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2201348

Country of ref document: CA

Ref country code: CA

Ref document number: 2201348

Kind code of ref document: A

Format of ref document f/p: F

WWP Wipo information: published in national office

Ref document number: 1995935104

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1995935104

Country of ref document: EP