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Design, synthesis and computational evaluation of a novel intermediate salt of N-cyclohexyl-N-(cyclohexylcarbamoyl)-4-(trifluoromethyl) benzamide as potential potassium channel blocker in epileptic paroxysmal seizures

Paper ID Volume ID Publish Year Pages File Format Full-Text
14886 1360 2016 10 PDF Available
Title
Design, synthesis and computational evaluation of a novel intermediate salt of N-cyclohexyl-N-(cyclohexylcarbamoyl)-4-(trifluoromethyl) benzamide as potential potassium channel blocker in epileptic paroxysmal seizures
Abstract

•A synthesis of novel intermediate salt of N-cyclohexyl-N-(cyclohexylcarbamoyl)-4-(trifluoromethyl) benzamide is reported.•Structures established on the basis of IR, 1H, 13C NMR Spectra and X-ray diffraction analysis.•Computational study on molecular docking and binding of the compound suggest, as the best potassium channel blocker in Blood Brain Barrier.•Resulting analogues have good oxygen enriching capacity.

The narrow therapeutic range and limited pharmacokinetics of available Antiepileptic drugs (AEDs) have raised serious concerns in the proper management of epilepsy. To overcome this, the present study attempts to identify a candidate molecule targeting voltage gated potassium channels anticipated to have superior pharmacological than existing potassium channel blockers. The compound was synthesized by reacting (S)-(+)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4] benzodiazepine5,11(10H,11aH)-dione with 4-(Trifluoromethyl) benzoic acid (C8H5F3O2) in DMF and N,N′-dicyclohexylcarbodiimide (DCC) which lead to the formation of an intermediate salt of N-cyclohexyl-N-(cyclohexylcarbamoyl)-4-(trifluoromethyl)benzamide with a perfect crystalline structure. The structure of the compound was characterized by FTIR, 1H NMR and 13C NMR analysis. The crystal structure is confirmed by single crystal X-ray diffraction analysis. The Structure-Activity Relationship (SAR) studies revealed that substituent of fluoro or trifluoromethyl moiety into the compound had a great effect on the biological activity in comparison to clinically used drugs. Employing computational approaches the compound was further tested for its affinity against potassium protein structure by molecular docking in addition, bioactivity and ADMET properties were predicted through computer aided programs.

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Keywords
Fluorinated N,N′-dicyclohexylcarbodiimide; X-ray structures; Molecular docking; ADMET property prediction; Paroxysmal seizures; K+ blocker
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Design, synthesis and computational evaluation of a novel intermediate salt of N-cyclohexyl-N-(cyclohexylcarbamoyl)-4-(trifluoromethyl) benzamide as potential potassium channel blocker in epileptic paroxysmal seizures
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Publisher
Database: Elsevier - ScienceDirect
Journal: Computational Biology and Chemistry - Volume 64, October 2016, Pages 64–73
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us