Use of analogues of polyisoprenyl pyrophosphate for inhibiting protein isoprenylation

摘要

The invention provides the use of a polyisoprenyl pyrophosphate analogue for preparing a pharmaceutical composition suitable for inhibiting protein isoprenylation. The polyisoprenyl pyrophosphate analogue may have formula 1, CHEM wherein: Pren represents a C54-C74 terpenoid group or a derivative thereof; A1, A2, A3 and A4 independently represent a direct bond or a C5-C8 alkylene or alkenylene group, optionally substituted; X1, X2, X3 and X4 independently represent a direct bond, oxygen, sulphur, imino or methylimino; Y1, Y2 and Y3 independently represent hydroxy, alkoxy, mercapto, alkylthio, amino, mono- or di-alkylamino, alkyl, alkenyl, alkynyl, cycloalkyl, aryl or arylalkyl, whereby one of Y1, Y2 and Y3 may also represent a C1/2 -C74 alkyl or alkenyl group; Z1 and Z2 independently represent oxygen or sulphur; and n is 0, 1 or 2, preferably 1; or a pharmaceutically acceptable salt thereof. The pharmaceutical composition is suitable for the prophylaxis and/or treatment of carcinomas and for the inhibition of the isoprenylation of a ras protein.