Experimental and computational studies of 1,5-diphenyl-pyrazole-3-carboxamide compounds as potential Cannabinoid receptor type 1


KOCA İ. , YAKAN M. , ÇAPAN İ., ŞAHİN E., SERT Y.

JOURNAL OF MOLECULAR STRUCTURE, vol.1264, 2022 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1264
  • Publication Date: 2022
  • Doi Number: 10.1016/j.molstruc.2022.133269
  • Title of Journal : JOURNAL OF MOLECULAR STRUCTURE
  • Keywords: Pyrazole, Thiazole, Carboxamide, Molecular docking, DRUG TARGET IDENTIFICATION, CYCLIC OXALYL COMPOUNDS, WEB SERVER, DERIVATIVES, ANTAGONIST, PYRAZOLE

Abstract

Cannabinoid type 1 (CB1) receptors play an important role in the pathophysiology of many diseases because of their regulatory roles in the central nervous system and peripheral organs. In this study, firstly, four new pyrazole-3-carboxamide derivatives with a structure similar to that of Rimonabant were synthesized. These compounds were identified by IR, 1 H NMR, 13 C NMR, HRMS and XRD analysis. Then, theoretical studies were carried out for the synthesized compounds. The electrophilic and nucleophilic attack sites of the four compounds were comprehensibly determined and evaluated using theoretical MEP analysis applied to the optimized structures. Additionally, the possible hydrogen bondings within the crystal structure were investigated by Hirsfeld surface analysis. Later, the theoretical best binding affinities of newly synthesized target compounds including thiazole ( 3a and 3c ) and thiadiazole ( 3b and 3d ) four molecules with four different targets such as 5TGZ (CB1 antagonist), 5ZTY (CB2), 1MMB (batimastat) and 4YXD (succinate dehydrogenase) proteins were performed using molecular docking simulations with AutoDockVina program in this report. Lastly, drug-likeness, ADME properties and the evaluation of toxicity parameters of newly synthesized molecules using smile codes were performed in detail. The findings revealed that the studied molecules may show potential bioactivity, especially as CB1 antagonists. (C) 2022 Elsevier B.V. All rights reserved.