WO1996031525A3 - Inhibitors of farnesyl-protein transferase - Google Patents

Inhibitors of farnesyl-protein transferase Download PDF

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Publication number
WO1996031525A3
WO1996031525A3 PCT/US1996/003974 US9603974W WO9631525A3 WO 1996031525 A3 WO1996031525 A3 WO 1996031525A3 US 9603974 W US9603974 W US 9603974W WO 9631525 A3 WO9631525 A3 WO 9631525A3
Authority
WO
WIPO (PCT)
Prior art keywords
farnesyl
ca1a2x
inhibitors
thiol
analogs
Prior art date
Application number
PCT/US1996/003974
Other languages
French (fr)
Other versions
WO1996031525A2 (en
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 EP96911382A priority Critical patent/EP0837857A4/en
Priority to AU54285/96A priority patent/AU713698B2/en
Priority to JP53033696A priority patent/JP2002504067A/en
Publication of WO1996031525A2 publication Critical patent/WO1996031525A2/en
Publication of WO1996031525A3 publication Critical patent/WO1996031525A3/en

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
    • 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
    • C07K5/0207—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)4-C(=0), e.g. 'isosters', replacing two amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Abstract

The present invention comprises analogs of the CA1A2X motif of the protein Ras that is modified by farnesylation in vivo. These CA1A2X analogs inhibit the farnesyl-protein transferase and the farnesylation of certain proteins. Furthermore, these CA1A2X analogs differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. The compounds of the instant invention also incorporate a cyclic amine moiety in the A2 position of the motif. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.
PCT/US1996/003974 1995-03-29 1996-03-25 Inhibitors of farnesyl-protein transferase WO1996031525A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP96911382A EP0837857A4 (en) 1995-03-29 1996-03-25 Inhibitors of farnesyl-protein transferase
AU54285/96A AU713698B2 (en) 1995-03-29 1996-03-25 Inhibitors of farnesyl-protein transferase
JP53033696A JP2002504067A (en) 1995-03-29 1996-03-25 Farnesyl-protein transferase inhibitors

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US41262695A 1995-03-29 1995-03-29
US41282895A 1995-03-29 1995-03-29
US08/412,626 1996-02-13
US08/412,828 1996-02-13

Publications (2)

Publication Number Publication Date
WO1996031525A2 WO1996031525A2 (en) 1996-10-10
WO1996031525A3 true WO1996031525A3 (en) 1996-12-27

Family

ID=27021839

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/003974 WO1996031525A2 (en) 1995-03-29 1996-03-25 Inhibitors of farnesyl-protein transferase

Country Status (1)

Country Link
WO (1) WO1996031525A2 (en)

Families Citing this family (2)

* 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
US5932590A (en) * 1996-12-05 1999-08-03 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase

Citations (2)

* 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
US5352705A (en) * 1992-06-26 1994-10-04 Merck & Co., Inc. Inhibitors of farnesyl protein transferase

Patent Citations (2)

* 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
US5352705A (en) * 1992-06-26 1994-10-04 Merck & Co., Inc. Inhibitors of farnesyl protein transferase

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
See also references of EP0837857A4 *
THE JOURNAL OF BIOLOGICAL CHEMISTRY, April 1993, Vol. 268, No. 11, GIBBS et al., "Selective Inhibition of Farresyl-Protein Transferase Blocks Ras Process in Vivo", pages 7617-7620. *

Also Published As

Publication number Publication date
WO1996031525A2 (en) 1996-10-10

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