Document Report Card

ID: ALA1142354

Journal: J Med Chem

Title: Synthesis and biological evaluation of (hetero)arylmethyloxy- and arylmethylamine-phenyl derivatives as potent P-glycoprotein modulating agents.

Authors: Colabufo NA, Berardi F, Perrone R, Rapposelli S, Digiacomo M, Vanni M, Balsamo A.

Abstract: Starting from lead compounds 12b and 28b, previously characterized as P-glycoprotein (P-gp) modulating agents, two series of new compounds were investigated. Compounds 14a, b and 15a, b displayed high P-gp modulating activity in the submicromolar range (EC 50 values from 0.25 to 0.80 microM). Moreover, amino derivatives 23- 27 showed EC 50 values ranging from 0.085 to 0.90 microM. In the pyridyl series, the best result has been obtained for 4-pyridyl derivative 17b (EC 50 = 0.85 microM). The best P-gp modulating agents 14a, b, 15a, b, and 23- 27 also have been studied for determining their breast cancer resistance protein (BCRP) inhibition activity. The results demonstrated that only the amino derivatives 23- 27 displayed moderate BCRP inhibition activity.

CiteXplore: 18257545

DOI: 10.1021/jm701267q