Quantitative structure activity relationship analysis of angiotensin II AT1 receptor antagonists

Abstract

The quantitative structure activity relationship (QSAR) models were developed using multiple linear regression (MLR) and partial least square (PLS) for a set of 85 AT1 receptor antagonists of hydantoin series. The MLR and PLS generated comparable models with good predictive ability and all the other statistical values, such as r, r2, \( {\text{r}}_{{({\text{cv}})}}^{2} , \) and F and s values, were satisfactory. The results obtained from this study indicate the importance of steric (K-alpha3), hydrophobic (log P, and total lipole), and total energy (Cosmic total energy) in determining the activity of AT1 receptor antagonists. The results clearly explained that optimum hydrophobicity of substituent at R2 position is favorable for the activity and presence of a substituent of particular size and shape on phenyl ring at R3 position is essential for the activity. This information is pertinent to the further design of new AT1 receptor antagonist containing the hydantoin nucleus.