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

摘要

The design, synthesis and α1-adrenoceptor antagonism of a series of bis-imidazoline (1a, 2a, 3a and 4a)Figure 2New families of compounds prepared in this work: (a) bis-2-iminoimidazolidinium derivatives, and (b) bis-guanidinium derivatives.Scheme 1 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 α1-adrenoceptors and found in the literature. Besides, a novel synthetic approach to the preparation of 2-(arylimino)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 α1 subtype targeted by this new family of compounds, they show an interesting profile as antagonists of α1-adrenoceptors and a new prototype, compound 1a, has been found deserving further development. Copyright (C) 2000 Elsevier Science Ltd.