Design, Synthesis and Biological Evaluation of New Imidazo[2,1-b]Thiazole Derivatives as Selective COX-2 Inhibitors

Mahsa Shahrasbi; Mahsa Azami Movahed; Orkideh Ghorban Dadras; Bahram Daraei; Afshin Zarghi

Design, Synthesis and Biological Evaluation of New Imidazo[2,1-b]Thiazole Derivatives as Selective COX-2 Inhibitors

Iran J Pharm Res. 2018 Fall;17(4):1288-1296.

Authors

Mahsa Shahrasbi¹, Mahsa Azami Movahed², Orkideh Ghorban Dadras¹, Bahram Daraei³, Afshin Zarghi²

Affiliations

¹ Department of Medicinal Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
² Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
³ Department of Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

PMID: 30568687
PMCID: PMC6269562

Abstract

A new series of imidazo[2,1-b]thiazole analogs containing a methyl sulfonyl COX-2 pharmacophore was synthesized and evaluated for their COX-2 inhibitory activity. According to in-vitro COX-1/COX-2 inhibition data, all compounds (6a-g) were selective inhibitors of COX-2 isoenzyme with IC₅₀ values in the highly potent 0.08-0.16 µM range. These results indicated that both potency and selectivity of COX-2 inhibitory activity were affected by the type and size of amine on C-5 of imidazo[2,1-b]thiazole ring. Our data identified N,N-dimethyl-1-(6-(4-(methylsulfonyl)phenyl)imidazo[2,1-b]thiazol-5-yl)methanamine (6a) as a potent and selective COX-2 inhibitor (IC₅₀ COX-1 >100 µM; IC₅₀ COX-2 = 0.08 µM; selectivity index = 313.7). Our results indicated that both potency and selectivity of COX-2 inhibitory activity were affected by the type and size of amine on C-5 of imidazo[2,1-b]thiazole ring.

Keywords: 1-b]Thiazole; Cyclooxygenase-2 inhibition; Design; Imidazo[2; Molecular modeling; Synthesis.