An overexpression of the transmembrane ATP-binding cassette transporter G2 
(ABCG2, BCRP) in cancer tissues is supposed to play a role in the multidrug 
resistance (MDR) of tumors resulting in an inefficient chemotherapy. Therefore, 
co-administration of selective and non-toxic ABCG2 inhibitors is a promising 
strategy for improving the efficacy of chemotherapy by blocking ABCG2-mediated 
export of the cytostatic drugs. In the present study, we designed a small 
library of 38 novel compounds containing a heteroaryl-phenyl scaffold possessing 
several (bioisosteric) moieties, and twelve new precursors. We investigated the 
library for ABCG2 inhibition, for the selectivity against MDR-involved efflux 
pump ABCB1 (P-gp) and for toxicity. Structure activity relationship (SAR) 
studies revealed that, at least a phenylheteroaryl-phenylamide scaffold is 
necessary for observing an ABCG2 inhibition. 
4-Methoxy-N-(2-(2-(6-methoxypyridin-3-yl)-2H-tetrazol-5-yl)phenyl)benzamide (43) 
exhibited a high potency (IC50 = 61 nM)), selectivity, low intrinsic toxicity 
and reversed the ABCG2-mediated drug resistance in presence of only 0.1 μM.