Discovery of biaryl anthranilides as full agonists for the high affinity niacin receptor.
Article Details
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Shen HC, Ding FX, Luell S, Forrest MJ, Carballo-Jane E, Wu KK, Wu TJ, Cheng K, Wilsie LC, Krsmanovic ML, Taggart AK, Ren N, Cai TQ, Deng Q, Chen Q, Wang J, Wolff MS, Tong X, Holt TG, Waters MG, Hammond ML, Tata JR, Colletti SL
Discovery of biaryl anthranilides as full agonists for the high affinity niacin receptor.
J Med Chem. 2007 Dec 13;50(25):6303-6. Epub 2007 Nov 10.
- PubMed ID
- 17994679 [ View in PubMed]
- Abstract
Biaryl anthranilides are reported as potent and selective full agonists for the high affinity niacin receptor GPR109A. The SAR presented outlines approaches to reduce serum shift and both CYPCYP2C8 and CYP2C9 liabilities, while improving PK and maintaining excellent receptor activity. Compound 2i exhibited good in vivo antilipolytic efficacy while providing a significantly improved therapeutic index over vasodilation (flushing) with respect to niacin in the mouse model.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Niacin Hydroxycarboxylic acid receptor 2 IC 50 (nM) 140 7.4 23 Details Niacin Hydroxycarboxylic acid receptor 2 EC 50 (nM) 1000 7.4 23 Details