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
Broxaterol 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 active
as the reference compounds. An electron-releasing group, probably
operating through a pi-pi interaction, in the 3-position of the
isoxazoline nucleus greatly enhances the affinity of the compounds.
Conversely, the closest analogs of Broxaterol (3-bromo
Delta(2)-isoxazolines 4a and 5a) are at least one order of magnitude
less active than the model compound 1. Throughout the series of
derivatives the anti stereoisomers are invariably more active than their
syn counterparts. (C) 1998 Elsevier Science Ltd. All rights reserved.