Discovery of novel antitumor antimitotic agents that also reverse tumor resistance.

ABSTRACT: We have discovered a novel series of 7-benzyl-4-methyl-5-[(2-substituted phenyl)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-2-amines, which possess antimitotic and antitumor activities against antimitotic-sensitive as well as resistant tumor cells. These agents bind to a site on tubulin that is distinct from the colchicine, vinca alkaloid, and paclitaxel binding sites and some, in addition to their antitumor activity, remarkably also reverse tumor resistance to antimitotic agents mediated via the P-glycoprotein efflux pump. The compounds were synthesized from N-(7-benzyl-5-ethynyl-4-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropanamide 11 or the corresponding 5-iodo analog 14 via Sonogashira couplings with appropriate iodobenzenes or phenylacetylene followed by reduction and deprotection t

SUBMITTER: Gangjee A 

PROVIDER: S-EPMC3858178 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature