Synthesis and structure-activity analysis of novel dihydropyridine derivatives to overcome multidrug resistance

The structure-activity relationships were studied on newly synthesized 1,4- dihydropyridine derivatives possessing a 1-pentyl group at the 4-position, and 3-pyridylpropylester was found to be one of the effective fragments for overcoming P-glycoprotein mediated multidrug-resistance (MDR) in cultured human cancer cells, in vitro. 3-Pyridylpropylester was also found to be one of the effective fragments for increasing the life span of P-glycoprotein overexpressing MDR P388 leukemia-bearing mice, in vivo. All compounds had w eak calcium antagonistic activities, but there appeared no relationship bet ween MDR reversing effect and calcium antagonistic activity. (C) 2001 Elsev ier Science Ltd. All rights reserved.