Abstract
The present communication deals with the Pharmacophore modeling, 3D QSAR and docking analysis on series of Pyrimidine derivatives as potential calcium channel blockers. The computational studies showed hydrogen bond donor, hydrogen bond acceptor, and hydrophobic group are important features for calcium channel blocking activity. These studies showed that Pyrimidine scaffold can be utilized for designing of novel calcium channels blockers for CVS disorders. Calcium ions plays a vital role in the cardiovascular sys- tem, they impart their action by acting on the calcium channels. The entry of calcium inside the cell can increase the vascular tone as well as heart rate and ultimately the blood pressure. The currently approved calcium channel blockers binds with L-type calcium channels located on the vascular smooth muscle, cardiac myocytes, and car- diac nodal tissue. These channels are responsible for reg- ulating the influx of calcium into muscle cells, 1�3 which in turn stimulates smooth muscle contraction and cardiac contraction. Therefore, by blocking calcium entry into the cell, will cause vascular smooth muscle relaxation (vasodi- lation), decreased myocardial force generation decreased heart rate (negative chronotropy), and decreased conduc- tion velocity within the heart (negative dromotropy) at the AV node. The 1,4-dihydropyridine (DHP) class of calcium channel blockers are widely utilized in the treatment of cardiovascular diseases such as hypertension, angina pec- toris and other spastic smooth muscle disorders. 4�6 The SAR of calcium channel blockers signifies the presence of ester linkage and electron withdrawing group like nitro and carbonyl groups. The Pyrimidine nucleus has been showing the various pharmacological activities like calcium channel blockers, anti cancer, antimicrobial, antiviral. In this com- munication an attempt is made to design and develop novel calcium channel blockers based on the Pyrimidine scaf- fold and identification of structure requirement of these molecules in the form of 3D descriptors and Pharmacoph- oric features for optimization of these ligands.
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