Bioorganic & Medicinal Chemistry 2005-02-15

Diphenylcyclohexylamine derivatives as new potent multidrug resistance (MDR) modulators.

Silvia Dei, Roberta Budriesi, Paiwan Sudwan, Marta Ferraroni, Alberto Chiarini, Arlette Garnier-Suillerot, Dina Manetti, Cecilia Martelli, Serena Scapecchi, Elisabetta Teodori

Index: Bioorg. Med. Chem. 13(4) , 985-98, (2005)

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Abstract

A series of compounds with a diphenylmethyl cyclohexyl skeleton, loosely related to verapamil, has been synthesized and tested as MDR modulators on anthracycline-resistant erythroleukemia K 562 cells. Their residual cardiovascular action (negative inotropic and chronotropic activity as well as vasorelaxant activity) was evaluated on guinea-pig isolated atria preparations and on guinea-pig aortic strip preparations. Most compounds of the series possess a good MDR-reverting activity together with a low cardiovascular action. Among them, compounds 3a1, 7a, and 8a are more potent than verapamil as MDR reverters and lack any cardiovascular action; they can represent useful leads for the development of new safe MDR reversing drugs.