Complex of ras-farnesyltransferase inhibitor and sulfobutylether-7-beta-cyclodextrin or 2-hydroxypropyl-beta-cyclodextrin and method

摘要

A ras-farnesyltransferase inhibitor complex formed of ras-farnesyltransferase inhibitor or a pharmaceutically acceptable salt thereof, of the formula Iwherein n is 0 or 1; R1 is selected from Cl, Br, phenyl, pyridyl or cyano; R2 is aralkyl; R3 is selected from lower alkyl, aryl or substituted aryl or heterocyclo; Z1 is selected from CO, SO2, CO2, or SO2NR5, R5 is selected from hydrogen, lower alkyl or substituted alkyl; and sulfobutylether-7-beta-cyclodextrin or 2-hydroxypropyl-beta-cyclodextrin is provided. The complex has unexpectedly high aqueous solubility of the ras-farnesyltransferase inhibitor and is useful for its intravenous delivery to humans with cancer. Also provided is a method for forming the complex. The ras-farnesyltransferase inhibitors are useful as anti-tumor agents.