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Sabakhi I, Topuzyan V, Hajimahdi Z, et al. Design, Synthesis and Biological Evaluation of New 1, 4-Dihydropyridine (DHP) Derivatives as Selective Cyclooxygenase-2 Inhibitors. Iran J Pharm Res. 2015;14(4):1087-93
Sabakhi, I., Topuzyan, V., Hajimahdi, Z., Daraei, B., Arefi, H., & Zarghi, A. (2015). Design, Synthesis and Biological Evaluation of New 1, 4-Dihydropyridine (DHP) Derivatives as Selective Cyclooxygenase-2 Inhibitors. Iranian journal of pharmaceutical research : IJPR, 14(4), 1087-93.
Sabakhi, Iman, et al. "Design, Synthesis and Biological Evaluation of New 1, 4-Dihydropyridine (DHP) Derivatives as Selective Cyclooxygenase-2 Inhibitors." Iranian journal of pharmaceutical research : IJPR vol. 14,4 (2015): 1087-93.
Sabakhi I, Topuzyan V, Hajimahdi Z, Daraei B, Arefi H, Zarghi A. Design, Synthesis and Biological Evaluation of New 1, 4-Dihydropyridine (DHP) Derivatives as Selective Cyclooxygenase-2 Inhibitors. Iran J Pharm Res. 2015;14(4):1087-93. PMID: 26664375; PMCID: PMC4673936.
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Iran J Pharm Res. 2015;14(4):1087-93.

Design, Synthesis and Biological Evaluation of New 1, 4-Dihydropyridine (DHP) Derivatives as Selective Cyclooxygenase-2 Inhibitors.

Iranian journal of pharmaceutical research : IJPR

Iman Sabakhi, Vigen Topuzyan, Zahra Hajimahdi, Bahram Daraei, Hadi Arefi, Afshin Zarghi

Affiliations

  1. Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical sciences, Tehran, Iran. ; The Scientific Thechnological Centre of Organic and Pharmaceutical Chemistry NASRAAL. Mnjoyan Institute of Fine Organic Chemistry, Yerevan, Armenia.
  2. The Scientific Thechnological Centre of Organic and Pharmaceutical Chemistry NASRAAL. Mnjoyan Institute of Fine Organic Chemistry, Yerevan, Armenia.
  3. Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical sciences, Tehran, Iran.
  4. Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

PMID: 26664375 PMCID: PMC4673936

Abstract

As a continuous research for discovery of new COX-2 inhibitors, chemical synthesis, in vitro biological activity and molecular docking study of a new group of 1, 4-dihydropyridine (DHP) derivatives were presented. Novel synthesized compounds possessing a COX-2 SO2Me pharmacophore at the para position of C-4 phenyl ring, different hydrophobic groups (R1) at C-2 position and alkoxycarbonyl groups (COOR2) at C-3 position of 1, 4-dihydropyridine, displayed selective inhibitory activity against COX-2 isozyme. Among them, compound 5e was identified as the most potent and selective COX-2 inhibitor with IC50 value of 0.30 μM and COX-2 selectivity index of 92. Molecular docking study was performed to determine probable binding models of compound 5e. The study showed that the p-SO2Me-phenyl fragment of 5e inserted inside secondary COX-2 binding site (Arg(513), Phe(518), Gly(519), and His(90)). The structure-activity relationships acquired reveal that compound 5e with methyl and ethoxycarbonyl as R1 and COOR2 substitutions has the necessary geometry to provide selective inhibition of the COX-2 isozyme and it can be a good basis for the development of new hits.

Keywords: 1; 4-Dihydropyridine (DHP) Derivatives; COX-2 Inhibitors; Molecular modeling; Synthesis

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