Sci Pharm. 2009; 77: 33–45.
Insight into the Structural Requirement of 2-Alkyl-4-(biphenylmethoxy)quinolines as Nonpeptide Angiotensin II Receptor Antagonists: A QSAR Approach
Vivek K. VYAS * 1, Anurekha JAIN 2, Suresh C. MAHAJAN 1, Radheshyam PATIDAR 1, Sunil MISTRY 1, Subhash C. CHATURVEDI 3
1 Mahakal Institute of Pharmaceutical Studies, Rajiv Gandhi Technical University Behind Air Strip Datana Deaws Road Ujjain 456664 (M.P.) India.
2 B. R. Nahata College of Pharmacy, Department of Medicinal Chemistry, Rajiv Gandhi Technical University, Mhow-Neemuch Road 458001 Mandsaur (M.P.) India.
3 School of Pharmacy Devi Ahilya Vishwavidylaya, Takshashila Parisar Khandwa road, 452003 Indore (M.P.) India.
* Corresponding author. E-mail: Vicky_1744@yahoo.com (V. K. Vyas).
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, F-test = 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
QSAR • Angiotensin II antagonists • Hypertension • AT1 and AT2 receptor
Received October 10th, 2008 | Accepted January 13th, 2009 | Published Online January 14th, 2009
