Document Report Card

ID: ALA1149093

Journal: J Med Chem

Title: Design and synthesis of new templates derived from pyrrolopyrimidine as selective multidrug-resistance-associated protein inhibitors in multidrug resistance.

Authors: Wang S, Wan NC, Harrison J, Miller W, Chuckowree I, Sohal S, Hancox TC, Baker S, Folkes A, Wilson F, Thompson D, Cocks S, Farmer H, Boyce A, Freathy C, Broadbridge J, Scott J, Depledge P, Faint R, Mistry P, Charlton P.

Abstract: In our continued effort to identify selective MRP1 modulators, we have developed two novel templates, 3 and 4, through rational drug design by identifying the key pharmacophore interaction at the 7-position of the pyrrolopyrimidine template 1. Further synthesis and SAR work on these novel templates gave a number of potent MRP1 modulators with great selectivity against Pgp. Additional studies to reduce the CYP3A4 inhibition are also reported. Several compounds of these classes were subjected to in vivo xenograft studies and in vivo efficacies were demonstrated.

CiteXplore: 14998324

DOI: 10.1021/jm0310129