Send Orders for Reprints to reprints@benthamscience.ae Open Pharmaceutical Sciences Journal, 2016, 3, 117-130 117 1874-8449/16 2016 Bentham Open Open Pharmaceutical Sciences Journal Content list available at: www.benthamopen.com/PHARMSCI/ DOI: 10.2174/1874844901603010117 RESEARCH ARTICLE Microwave Assisted Facile Synthesis and Biological Evaluation of Novel 2-Indolyl -1, 5-Benzothiazepines Anna P. G. Nikalje *, a , Mangesh S. Ghodke b , Firoz A. K. Khan a and Jaiprakash N. Sangshetti a a Department of Pharmaceutical Chemistry, Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431003 (M.S.) India b Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education & Research, Shirpur-425405, Dhule (M.S.) India Received: June 11, 2015 Revised: March 21, 2016 Accepted: March 25, 2016 Abstract: Background: The research work reports facile, eco-friendly microwave- assisted solvent free synthesis of coupled heterocyclic system 2-(1H- indol-3-yl)-4-substitued-2, 3-dihydrobenzo [1, 5] thiazepine derivatives obtained by cyclo condensation of 1-substituted-3(1H- indolyl)-2-propen-1-ones with 2-amino thiophenol in presence of eco-friendly catalyst zirconium(IV) oxy chloride, in solvent-free conditions. The reaction was completed in 3-6 minutes and gives better yields than the conventional synthesis which requires 6-8 hrs. Result and Conclusion: The newly synthesized compounds were evaluated for antihypertensive activity in Sprague- Dawley rats by tail- cuff method and compared with diltiazem, the standard antihypertensive drug. The data suggested that some of the compounds of the current series exhibited enhanced antihypertensive activity than the standard. As benzothiazepines are bioisosters of benzodiazepines, the synthesized novel indolyl-benzothiazepine derivatives were also screened for CNS activities such as CNS depressant activity by actophotometer and anticonvulsant activity by MES and PTZ model on mice. The title compounds have exhibited good CNS depression and anticonvulsant activity. The compounds thus have shown dual antihypertensive and CNS depressant, anticonvulsant activity and are biologically potential molecules. The molecular docking was performed for the synthesized compounds to assess their binding affinities to GABA-A receptor in order to rationalize their anticonvulsant activities in a qualitative way. Keywords: 1, 5-benzothiazepine, Antihypertensive activity, CNS depressant, MES, Microwave-assisted, PTZ. INTRODUCTION Over the last several decades, tremendous advances in basic and clinical research on cardiovascular disease have greatly improved the prevention and treatment of the cardiovascular diseases, the nation's number one killer of men and women of all races [1, 2]. Hypertension is a multi factorial disease frequently associated with other cardiovascular problems. None of the antihypertensive drugs available can cure all cases of hypertension. This situation causes a unique scenario in this area of therapeutic research: less recent approaches, which make use of drugs acting on the adrenergic system, diuretics, calcium antagonists, nitro-vasodilators and so on, have not yet been abandoned, while new compounds are still being developed today. Excessive vasodilatation results in hypotension, dizziness and headache Dihydropyridines are often associated with tachycardia and chest pain, whereas verapamil and diltiazem may cause bradycardia, also associated with additive cardio depressive effects. Keeping inview the present stressful lifestyle, * Address correspondence to this author at the Department of Pharmaceutical Chemistry, Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Rauza Bagh, P.B. No. 33, Aurangabad, Maharashtra 431001, India; Fax: +91 0240 2381129; E-mail: annapratimanikalje@gmail.com