A QSAR study on 2-(4-methylpiperazin-1-yl)quinoxalines as human histamine H4 receptor ligands

Abstract

The histamine H4 receptor binding affinity of 2-(4-methylpiperazin-1-yl)quinoxaline derivatives has been quantitatively analyzed in terms of Dragon descriptors. The derived QSAR models have provided rationales to explain the activity of titled derivatives. The descriptors identified in CP-MLR analysis have highlighted the role of path/walk 4-Randic shape index (PW4), mean square distance (MSD) index, topological charges (GGI9, JGI2, and JGI7), atomic properties in respective lags of 2D-autocorrelations (MATS7e, GATS7e, and MATS8p), and Burden matrix (BELm1) to explain the binding affinity. Certain structural fragments (C-002 and C-027) have also shown prevalence to optimize the H4R binding affinity of titled compounds. The PLS analysis has also confirmed the dominance of information content of CP-MLR-identified descriptors for modelling the activity. © 2011 Informa UK, Ltd.