Insight into the Structural Requirement of 2-Alkyl-4-(biphenylmethoxy)quinolines as Nonpeptide Angiotensin II Receptor Antagonists: A QSAR Approach

Abstract

In the current study a quantitative structure activity relationship approach using sequential multiple linear regression analysis was applied to a series of 2-alkyl-4-(biphenylylmethoxy)quinolines as angiotensin II (Ang II) receptor antagonists by using Chem 3D and Dragon Software. The studies, carried out on 33 analogs, give statistically significant correlations of selective Ang II antagonistic activity with physical properties concerning size, symmetry, shape and distribution of molecule atoms. Among several 2D quantitative structure activity relationship models, one model gave good statistical significance (r > 0.81, Ftest = 10.47, S < 0.30, chance correlation < 0.01). 3D QSAR studies show that Hennery's law constant, Dipole and VDWE play a significant role in Ang II antagonistic activity. These QSAR studies help us in the design and prediction of novel substituted benzimidazole Ang II receptor antagonists. Keywords

Homology modeling, binding site identification and docking study of human angiotensin II type I (Ang II-AT1) receptor

“…In the year 2009 [10], we have performed a QSAR study on 2-alkyl-4-(biphenylmethoxy)quinolone derivatives as angiotensin II receptor antagonists; then, in the year 2011 [9], we have compiled the literature of substituted benzimidazole derivatives as Ang II-AT 1 receptor antagonist in a review paper. In the year 2013 [11], we have performed CoMFA and CoMSIA study on substituted benzimidazole derivatives as ARBs, and based upon in silico design, [12] we have synthesized substituted benzimidazole derivatives and screened them as Ang II-AT 1 receptor antagonists in the year 2014.…”