Open Pharmaceutical Sciences Journal
2016, 3 : 117-130Published online 2016 June 22. DOI: 10.2174/1874844901603010117
Publisher ID: PHARMSCI-3-117
RESEARCH ARTICLE
Microwave Assisted Facile Synthesis and Biological Evaluation of Novel 2-Indolyl -1, 5-Benzothiazepines
b Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education & Research, Shirpur-425405, Dhule (M.S.) India
* 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
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.