Abstract: Three dimensional structure activity relationships of γ- hydroxy butenolide endothelin antagonists were studied using CoMFAtechnique. Besides the steric and the electrostatic fields, the Hbond field was introduced into the computations. The QSARresults showed that the introduction of the Hbond field improved the quality of the obtained CoMFAmodel obviously. The model can forecast not only the compounds in the training set but also the compounds in the test set. The CoMFAcontour plots identified several key features including steric, electrostatic and Hbond fields, which were valuable for us to get insight into the potential mechanisms of the intermolecular interactions between inhibitor and receptor. Suitable steric and electrostatic effects as well as Hbond donor and acceptor are required for a higher activity.

Key words: Hydroxy butenolide, Endothelin, Antagonists, Comparative molecular field analysis(CoMFA)