Comparative molecular field analysis of gamma-hydroxy butenolide endothelin antagonists

Three dimensional structure-activity relationships of gamma -hydroxy buteno lide endothelin antagonists were studied using CoMFA technique. Besides the steric and the electrostatic fields, the H-bond field was introduced into the computations. The QSAR results showed that the introduction of the H-bo nd field improved the quality of the obtained CoMFA model obviously. The mo del can forecast not only the compounds in the training set but also the co mpounds in the test set. The CoMFA contour plots identified several key fea tures including steric, electrostatic and H-bond fields, which were valuabl e for us to get insight into the potential mechanisms of the intermolecular interactions between inhibitor and receptor. Suitable steric and electrost atic effects as well as H-bond donor and acceptor are required for a higher activity.