Design, synthesis, and in vivo activity of novel inhibitors of delta-5 desaturase for the treatment of metabolic syndrome.

Autor: Baugh SD; Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States. Electronic address: simondpbaugh@gmail.com., Pabba PK; Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States., Barbosa J; Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States., Coulter E; Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States., Desai U; Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States., Gay JP; Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States., Gopinathan S; Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States., Han Q; Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States., Hari R; Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States., Kimball SD; Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States., Nguyen HV; Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States., Ni CY; Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States., Powell DR; Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States., Smith A; Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States., Terranova KM; Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States., Wilson A; Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States., Yu XC; Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 7738, United States., Lombardo VK; Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2015 Sep 15; Vol. 25 (18), pp. 3836-9. Date of Electronic Publication: 2015 Jul 26.
DOI: 10.1016/j.bmcl.2015.07.066
Abstrakt: The synthesis, SAR, and in vivo activity of inhibitors of delta-5 desaturase are described. Ring-constraint of the initial series provided access to a variety of in vitro active chemotypes, from which the indazole was selected. Examples from the indazole series displayed in vivo activity in reducing the enzymatic activity of liver delta-5 desaturase.
(Copyright © 2015 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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