Synthesis, characterization, and pharmacological evaluation of benzothiopyran derivatives as a novel class of calcium ch
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Med Chem Res (2013) 22:2188–2195 DOI 10.1007/s00044-012-0211-y
ORIGINAL RESEARCH
Synthesis, characterization, and pharmacological evaluation of benzothiopyran derivatives as a novel class of calcium channel blockers Rajkumari Nalwaya • Arvind Sahai • Subhash Chander • Manish Sharma • Ruchi Malik • Gaurav Sarsodia
Received: 27 June 2011 / Accepted: 20 August 2012 / Published online: 19 September 2012 Ó Springer Science+Business Media, LLC 2012
Abstract The current research aimed to investigate the importance of the heterocyclic ring system in the structure of the cardiovascular drug Diltiazem for its calcium channel blocking activity. The manuscript describes the design, synthesis, and biological testing of Benzothiopyran derivatives (7a–7f). The new compounds maintain some Diltiazem pharmacophores. Benzothiopyran has two pharmacophore: the aromatic benzene ring fused with the heterocyclic thiopyrans ring, and the stereo-chemical centers (alkyl ether). In vitro evaluation of Benzothiopyran derivatives (7a–7f) for calcium channel blocking effects revealed moderate activities. Compounds of the current series showed optimum activity when the alkyl ether chain was substituted on the 3-chloro-3,4-dihydro-2H-1-benzothiopyran-4-ol derivatives (7a–7f). Keywords Calcium channel blocker Diltiazem Benzothiopyran Cardiovascular agents
Introduction Calcium channel blockers (CCBs) are a group of heterogeneous drugs whose main pharmacological effect is to prevent or reduce the entry of calcium into cell via specialized calcium channel (Gennaro, 2000; Mehanna and R. Nalwaya S. Chander (&) M. Sharma R. Malik G. Sarsodia Department of Medicinal Chemistry, TIFAC-CORE, Innovator Square, B. R. Nahata College of Pharmacy, Mandsaur, M.P., India e-mail: [email protected] A. Sahai Government P.G. College, Mandsaur, M.P., India
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Kim, 2003). Commercially available calcium channel blockers belong to either one of three chemical classes: Dihydropyridines (Amlodipine, Nifedipine, Felodipine, Isradipine), Phenyl alkyl amines (Verapamil, Gallopamil), and Benzothiazepine (Diltiazem) (Delgado and Remers, 1998). The intracellular concentration of calcium plays an important role in maintaining the tone of smooth muscle and in the contraction of the myocardium. Calcium enters muscle cells through special voltage-sensitive calcium channels. Calcium channel antagonists block the inward movements of calcium by binding it to L-type calcium channels in the heart and in smooth muscle of the coronary and peripheral vasculature (Harvey et al., 2000). These antagonists prevent the calcium ions needed for muscle contraction from entering the cells of smooth and cardiac muscle. This decreases intracellular calcium leading to a reduction in muscle contraction. In heart, a decrease in calcium available for each beat results in decreased cardiac contractility. The current research explores the development of new and facile synthetic methods for such heterocyclic considered for activity (Rios et al., 2006). Benzothiopyran is a heterocycl
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