Analogs of a 4-aminothieno[2,3-d]pyrimidine lead (QB13) as modulators of P-glycoprotein substrate specificity.

P-glycoprotein (P-gp) is an important factor in the development of multidrug resistance (MDR) in cancer cells. In literature reports, a thieno[2,3-d]pyrimidine (QB13) was described as P-gp modulator and opposed effects on the cell accumulation of distinct P-gp substrates were postulated. On the basis of this lead structure, a series of 2-alkylthio-4-aminothieno[2,3-d]pyrimidines was prepared and tested in a daunorubicin accumulation assay. Modulation of substrate specificity was shown for selected compounds in cytotoxicity (MTT) assays.