Bioorganic & Medicinal Chemistry Letters 2010-10-15

Search for influence of spatial properties on affinity at α1-adrenoceptor subtypes for phenylpiperazine derivatives of phenytoin.

Jadwiga Handzlik, Heinz H Pertz, Tilo Görnemann, Sven Jähnichen, Katarzyna Kieć-Kononowicz

Index: Bioorg. Med. Chem. Lett. 20(20) , 6152-6, (2010)

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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.Copyright © 2010 Elsevier Ltd. All rights reserved.