New pyrimidine/thiazole hybrids endowed with analgesic, anti‐inflammatory, and lower cardiotoxic activities: Design, synthesis, and COX‐2/sEH dual inhibition. Issue 7 (15th April 2022)

• Record Type: Journal Article
• Authors: Abdel‐Aziz, Salah A.; Taher, Ehab S.; Lan, Ping; El‐Koussi, Nawal A.; Salem, Ola I. A.; Gomaa, Hesham A. M.; Youssif, Bahaa G. M.
• Is Part Of: Archiv der Pharmazie. Volume 355:Issue 7(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-04-15
• Subjects: anti‐inflammatory -- COX‐2 -- pyrimidine -- sEH -- thiazole -- ulcer; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.202200024
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: Some cyclooxygenase (COX)‐2 selective medications were withdrawn from the market just a few years after their production due to cardiovascular side effects. In this study, a new series of pyrimidine/thiazole hybrids 7a–p was synthesized as selective COX‐2/soluble epoxide hydrolase (sEH) inhibitors with analgesic and anti‐inflammatory effects, and lower cardiotoxicity effects. The target compounds were synthesized and in vitro tested against COX‐1, COX‐2, and sEH enzymes. Hybrids 7j, 7k, and 7i showed the greatest COX‐2‐inhibitory activity and were discovered to be the most potent dual COX‐2/sEH inhibitors. In vivo tests revealed that these hybrids were the most active analgesic/anti‐inflammatory agents, with improved ulcerogenic and cardioprotective properties. Finally, the most active dual inhibitors were docked into COX‐2/sEH active regions to explain their binding mechanisms. Abstract : A new series of pyrimidine/thiazole hybrids (7a–p ) were synthesized as selective cyclooxygenase‐2 (COX‐2)/soluble epoxide hydrolase (sEH) inhibitors with analgesic and anti‐inflammatory effects, and lower cardiotoxicity effects. Hybrids 7j, 7k, and 7i were discovered to be the most potent dual COX‐2/sEH inhibitors, as well as the most active analgesic/anti‐inflammatory agents.