Comparative molecular field analysis of some pyridazinone-containing alpha(1)-antagonists

Diverse series of piperazines linked at N1 to 4, 5, or 6 positions of 3-(2H )-pyridazinone ring and at N4, by a suitable alkyl spacer, to some classica l alpha(1)-adrenoceptor pharmacophore moieties, were tested in vitro for th eir alpha(1)-adrenoceptor antagonist activity. The modeling of their biolog ical activity (pK(b)) by comparative molecular held analysis led to the dev elopment of a statistically significant partial least squares (PLS) model a ble to detect at 3-D level the main physicochemical interactions responsibl e for alpha(1)-adrenoceptor antagonist activity. (C) 1999 Published by Else vier Science Ltd. All rights reserved.