The design, synthesis and a1-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 ful®l the conditions of the most recent pharmaco- phore proposed for a1-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 a1 subtype targeted by this new family of compounds, they show an interesting pro®le as antagonists of a1-adrenoceptors and a new prototype, compound 1a, has been found deserving further development

The authors thank the Spanish DGICYT (Project No. SAF 97-0044) for ®nancial support. One of us (CD) is a holder of a Marie Curie Research Training Grant for which he thanks the European Commission, Directorate General XII (Science, Research and Development)

Peer reviewed