A Selective Pharmacophore Model for β₂-Adrenoceptor Agonists

Abstract: β₂-Adrenoceptor selectivity is an important consideration in drug design in order to minimize the possibility of side effects. A selective pharmacophore model was developed based on a series of selective β₂-adrenoceptor agonists. The best pharmacophore hypothesis consisted of five chemical features (one hydrogen-bond acceptor, one hydrogen-bond donor, two ring aromatic and one positive ionizable feature). The result was nearly in accordance with the reported interactions between the β₂-adrenoceptor and agonists, and it shared enough similar features with the result of field point patterns by FieldTemplater, which mainly validated the pharmacophore model. Moreover, the pharmacophore could predict the selectivity over the β₁-adrenoceptor. These results might provide guidance for the rational design of novel potent and selective β₂-adrenoceptor agonists.