Predictive QSAR modeling of substituted Phenylpyrazinones as corticotropin-releasing factor-1 (CRF1) receptor antagonists: computational approach

Abstract

A QSAR study has been performed on a series of Phenylpyrazinones derivatives with potent corticotropin-releasing factor-1 (CRF1) receptor antagonists. Structural features responsible for the activity of the compounds were characterized by using physicochemical, topological, and electrotopological descriptors, calculated from the Molecular Design Suite software. The statistically significant 2D-QSAR model having r 2 = 0.8141 and q 2 = 0.7391 with pred_r 2 = 0.7827 was developed by partial least squares method. Results reveal that the 2D-QSAR studies signify positive contribution of SsOHcount and SsCH3 count toward the biological activity, whereas negative contribution of 1PathCoun will be in favor of higher CRF1 activity. The QSAR model indicated that the T_2_F_1, T_C_Cl_1 and SaasCE-index played an important role in determining CRF1 receptor antagonists. Their corticotropin-releasing factor 1 capacity can be increased by number and position of the chlorine group. These correlations will be helpful in the development of Phenylpyrazinones as CRF1 receptor activities with a much more enhanced potency.