Design, synthesis, molecular modeling and biological evaluation of novel diaryl heterocyclic analogs as potential selective cyclooxygenase-2 (COX-2) inhibitors

Deema A Al-Turki; Mohamed A Al-Omar; Laila A Abou-Zeid; Ihsan A Shehata; Mohammed S Al-Awady

doi:10.1016/j.jsps.2015.07.001

Design, synthesis, molecular modeling and biological evaluation of novel diaryl heterocyclic analogs as potential selective cyclooxygenase-2 (COX-2) inhibitors

Saudi Pharm J. 2017 Jan;25(1):59-69. doi: 10.1016/j.jsps.2015.07.001. Epub 2015 Jul 26.

Authors

Deema A Al-Turki¹, Mohamed A Al-Omar¹, Laila A Abou-Zeid², Ihsan A Shehata³, Mohammed S Al-Awady⁴

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, P.O. Box 2457, King Saud University, Riyadh 11451, Saudi Arabia.
² Department of Organic Pharmaceutical Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
³ Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
⁴ Department of Pharmacology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.

Abstract

New series of 3,4-diaryl-2-thioxoimidazolidin-4-ones and 3-alkylthio-4,5-diaryl-4H-1,2,4-triazoles were designed, synthesized and evaluated for their activity as anti-inflammatory agents. Compounds 20, 21, 23 and 34 are highly selective inhibitors of COX-2 enzyme at a concentration of 100 mM relative to celecoxib, the standard reference. (±)-3-(4-Phenoxy-phenyl)-5-phenyl-2-thioxoimidazolidin-4-ones 23 exhibited the most active anti-inflammatory agent.

Keywords: Anti-inflammatory; Docking; Selective COX-2 inhibitors; Synthesis.