Use of amphiphilic anions for the reduction of the cytostatics - resistance due to inhibition of the imparted by the mrp - protein membrane transports

摘要

The use of phenoxy-alkoxy cpds. of formula (I) or their salts for the treatment of cancer is new. R1 = CH3-CO- or y substd. phenyl; Y= H or halo; R2 = H, OH or OCH3; R3 = 1-6C alkyl; R4 = H, OH or OCH3; n = 3-5; A= a gp. of formula (i) or (ii); R5 = H, 1-6C alkyl, 2-5C alkenyl, 2-5C alkynyl, benzyl or phenyl; R6 = H or halo; R7 = COOH or 5-tetrazolyl; T = a bond, CH2, O, CO or S(O)q; q = 0-2; provided that when one of R2 and R4 is OH or OCH3, the other of R2 and R4 must be H. Also claimed are: (A) the use of amphiphilic anions having a mol.wt. of 300-950 daltons for inhibiting the membrane transport mediated by the multidrug resistance (MDR)-associated protein (MRP); (B) a test kit for measuring the inhibition of MRP, contg. membrane vesicles, ATP and radioactively labelled leukotrienes C4, D4 and/or E4 or fluorescent structural analogues of leukotriene C4, D4 and/or E4; (C) a method for reversing MRP-mediated multiple drug resistance comprising administering a MRP reversal agent; (D) a method for reversing MRP-mediated multiple drug resistance comprising administering a cpd. of formula (I) or their salts; (E) a process for identifying cpds. which reverse MRP-mediated multiple drug resistance comprising evaluating a test cpd. for its ability to diminish MRP-mediated transport of leukotrienes or structural analogues.