Method for the treatment of diseases related with protein isoprenylation

摘要

The invention provides a method for inhibiting protein isoprenylation by administration of a polyisoprenyl pyrophosphate analogue. The polyisoprenyl pyrophosphate analogue may have formula 1, <IMAGE> 1. wherein: Pren represents a C10-C30 terpenoid group or a derivative thereof; A1, A2, A3 and A4 independently represent a direct bond or a C1-C4 alkylene or alkenylene group, optionally having substituents selected from methyl, hydroxy, methoxy, mercapto, methylthio, amino, methylamino, dimethylamino, halogen and a group having formula -X5-A5-P(=Z2)Y2Y3; A5 represents a direct bond or a C1-C4 alkylene or alkenylene group; X1, X2, X3, X4 and X5 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 C7-C30 alkyl or alkenyl group or a group having formula -X5-A5-P(=Z2)Y2Y3 and two of Y1, Y2 and Y3 may together represent an oxygen or sulfur atom or an imino or methylene group; Z1 and Z2 independently represent oxygen or sulphur; and n is 0, 1 or 2; or a pharmaceutically acceptable salt thereof. The invention further provides a pharmaceutical composition containing such a polyisoprenyl pyrophosphate analogue, which composition is suitable for the treatment of carcinomas such as by the inhibition of the isoprenylation of a member of the ras protein family.