Synthesis of new 1-(2-, 3-, or 4-methanesulfonylphenyl)-2-[5-(N-hydroxypyridin-2(1H)-one)]acetylene regioisomers: A search for novel cyclooxygenase and lipoxygenase inhibitors

✍ Scribed by Morshed A. Chowdhury; Hua Chen; Khaled R. A. Abdellatif; Ying Dong; Kenneth C. Petruk; Edward E. Knaus

• Publisher: Journal of Heterocyclic Chemistry
• Year: 2009
• Tongue: English
• Weight: 84 KB
• Volume: 46
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.23

✦ Synopsis

Abstract

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A group of acetylene regioisomers were designed such that a cyclooxygenase‐2 (COX‐2) SO~2~Me pharmacophore was located at the ortho‐, meta‐, or para‐position of the acetylene C‐1 phenyl ring, and an iron‐chelating 5‐lipoxygenase (5‐LOX) N‐hydroxypyridin‐2(1__H__)‐one moiety was attached via its C‐5 position to the C‐2 position on an acetylene template (scaffold). These target linear acetylene regioisomers were synthesized via a palladium‐catalyzed Sonogashira cross‐coupling reaction. Structure‐activity data acquired using in vitro cell‐based inhibition assays indicated that this novel class of 1‐(2‐, 3‐, or 4‐methanesulfonylphenyl)‐2‐[5‐(N‐hydroxypyridin‐2(1__H__)‐one)]acetylene regioisomers did not inhibit the COX‐2 or (5‐LOX) enzymes, and that they are devoid of in vivo anti‐inflammatory activities. J. Heterocyclic Chem., 46, 58 (2009).