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Part-IIIAdvances Dihydropyridines and …ROROH 3 COOOOH 3 C N CH 3R 1H 3 COOOR 3NHH 3 C N CH 3R 2R 25758Figure-9. Structures of 57 and 58 DHPs.In continuation to this, new N-alkylated 1,4- DHPs derivatives were synthesized and theirability to overcome MDR was examined in vincristine-resistant P388 cells (P388/VCRcells). DHPs that possessed an arylalkyl substituent on the DHPs ring nitrogen 59, 60, 61were more potent than verapamil in potentiating the cytotoxicity of vincristine againstP388/VCR cells. However, neither drug effectively enhanced the antitumor activity ofvincristine in tumor-bearing mice. Introduction of basic nitrogen-containing substituentson the side chain of 1,4- DHPs gave improved activity in vitro and in vivo. The piperazinederivative 62 and 63 were more than 10 times as potent as verapamil in vitro. Fourcompounds 64, 65, 66 and 67 selected for in vivo testing showed superior antitumoractivity in P388/VCR-bearing mice in combination with vincristine. The SARs of thecompounds are discussed. 89413