IDENTIFICATION OF A DIHYDROPYRIDINE AS A POTENT ALPHA(1A) ADRENOCEPTOR-SELECTIVE ANTAGONIST THAT INHIBITS PHENYLEPHRINE-INDUCED CONTRACTIONOF THE HUMAN PROSTATE

A number of novel dihydropyridine derivatives based upon carbonyl)-2,6 -dimethyl-4-(4-nitrophenyl)-5-((3-(4, iphenylpiperdin-1-yl)propyl)amin ocarbonyl)pyridine (4) have been synthesized and tested at cloned huma n a adrenoceptors as well as the rat L-type calcium channel. Within th is compound series, bonyl)-1,4-dihydro-2,6-dimethyl-4-(4-nitrophenyl)- phenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (19) displayed goo d binding affinity and selectivity for the alpha(1a) adrenoceptor (pK( i) = 8.73) and potently inhibited (pA(2) = 9.23) phenylephrine-induced contraction of the human prostate.