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.
Synthesis of new Delta(2)-isoxazoline derivatives and their pharmacological characterization as beta-adrenergic receptor antagonists / P. Conti, C. Dallanoce, M. De Amici, C. De Micheli, K.N. Klotz. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 6:4(1998), pp. 401-408.
|Titolo:||Synthesis of new Delta(2)-isoxazoline derivatives and their pharmacological characterization as beta-adrenergic receptor antagonists|
CONTI, PAOLA (Primo)
DALLANOCE, CLELIA MARIANGIOLA LUISA (Secondo)
DE MICHELI, CARLO (Penultimo)
|Parole Chiave:||synthesis; binding affinity; adrenergic antagonists; Broxaterol analogs; Falintolol analogs|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||1998|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/S0968-0896(97)10051-7|
|Appare nelle tipologie:||01 - Articolo su periodico|