Overexpression of breast cancer resistance protein (BCRP/ABCG2) has been shown to play an important role in the development of resistance to various anticancer agents. A series of BCRP/ABCG2 inhibitors with an amide group between rings A and B (benzamide series) and amide or urea linker between rings B and C were previously synthesized and evaluated in our lab. Two of the analogues in the benzamide series exhibited an activity that was comparable to that of the known ABCG2 inhibitor, Fumitremorgin C (FTC), and were selective against ABCB1 overexpresssing KB-C2 cells. In the present study, a series of phenyl tetrazole derivatives with an amide or urea linker between rings B and C along with various substitutions at R<sub>1</sub> and R<sub>2</sub> positions has been synthesized. The results of their ABCG2 inhibitory activity using drug resistant H460/MX20 cells and selectivity against ABCB1 protein in KB-C2 cells along with their effects on the ATPase enzyme using ABCG2 overexpressed membranes will be presented.

Synthesis and evaluation of phenyl tetrazole derivatives with amide or urea linkers as BCRP/ABCG2 inhibitors

253rd National Meeting (2017)

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