SYNTHESIS OF NEW DELTA(2)-ISOXAZOLINE DERIVATIVES AND THEIR PHARMACOLOGICAL CHARACTERIZATION AS BETA-ADRENERGIC-RECEPTOR ANTAGONISTS

A series of Delta(2)-isoxazoline derivatives structurally related to B roxaterol 1 and Falintolol 3 has been prepared and evaluated for their binding affinity to beta(1)- and beta(2)-adrenergic receptors. Among the tested compounds only the 3-isopropenyl anti derivative 4d is as a ctive as the reference compounds. An electron-releasing group, probabl y operating through a pi-pi interaction, in the 3-position of the isox azoline nucleus greatly enhances the affinity of the compounds. Conver sely, the closest analogs of Broxaterol (3-bromo Delta(2)-isoxazolines 4a and 5a) are at least one order of magnitude less active than the m odel compound 1. Throughout the series of derivatives the anti stereoi somers are invariably more active than their syn counterparts. (C) 199 8 Elsevier Science Ltd. All rights reserved.