Search for influence of spatial properties on affinity at α 1-adrenoceptor subtypes for phenylpiperazine derivatives of phenytoin

Abstract

A series of phenylpiperazine derivatives of phenytoin was evaluated for their affinity at α 1-adrenoceptor subtypes in functional bioassays (rat tail artery: α 1A and/or α 1B; guinea pig spleen: α 1B; rat aorta: α 1D). The most potent compounds at α 1A-, α 1B- and α 1D-adrenoceptors, 11, 18 and 8, showed affinities in the submicromolar range. The role of a hydrogen bond donor group for affinity and selectivity at α 1B-adrenoceptors, postulated by Bremner’s pharmacophore model, was confirmed by functional and molecular modelling studies.