A Selective Pharmacophore Model for β2-Adrenoceptor Agonists

Molecules

Rui-Juan Xing¹  Jian Wang¹  Li Pan¹ 

[1] Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China

关键词: β₂-adrenoceptor agonists;    selectivity;    pharmacophore;    molecular field-based similarity;   

DOI  :  10.3390/molecules14114486

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.