Novel inhibitors of prenylated pyrophosphate consuming enzymes

摘要

The invention pertains to new tripeptide and tetrapeptide analogs suitable as an inhibitor of a prenylpyrophosphate-consuming enzyme complying with formula A-B-B'-D, in which formula: A is Ap-(CH2)0-3-Z<1>-(CH2)0-3-Z<2>-(CHR<1>)0-1-CO- B and B' are each independently a residue of a natural or unnatural amino acid, or B and B' together are a residue of a single non-natural amino acid having a cyclic unit; D is -NH-CH(COX)-R<2 >or D is -NH-CH(COX)-(CH2)0-2-R<5 > wherein Ap is an optionally substituted C5-C14 hydrocarbon group, R<1 >is hydrogen or an optionally substituted C1-C4 alkyl group, R<2 >is a C1-C4 alkyl group substitued with an acid group, R<5 >is an optionally substituted aromatic or heterocyclic group, X is hydroxy or amino or their derivatives and Z<1 >and Z<2 >are direct bonds or spacer groups. The invention further pertains to pharmaceutical compositions containing these peptide analogs and to methods for treatment of conditions requiring inhibition of protein-prenyl transferase activity and methods for assaying protein-prenyl transferase activity.