New aromatic iminoimidazolidine derivatives as α1-adrenoceptor antagonists:: A novel synthetic approach and pharmacological activity

The design, synthesis and alpha(1)-adrenoceptor antagonism of a series of bis-imidazoline (1a, 2a, 3a and 4a) and bis-guanidine (1b, 2b, 3b and 4b) diphenyl derivatives are reported. All of these compounds fulfil the conditions of the most recent pharmacophore proposed for alpha(1)-adrenoceptors and found in the literature. Besides, a novel synthetic approach to the preparation of 2-(aryl-imino)imidazolidine derivatives is described. All the tested compounds, except the bis-guanidinium derivative 3b, inhibit the contractile responses induced by noradrenaline in aortic rings of rat and rabbit in a dose-dependent manner. Our results indicate that, even though some discrepancies are observed in terms of the alpha(1) subtype targeted by this new family of compounds, they show an interesting profile as antagonists of alpha(1)-adrenoceptors and a new prototype, compound 1a, has been found deserving further development. (C) 2000 Elsevier Science Ltd. All rights reserved.