Discovery of biaryl anthranilides as full agonists for the high affinity niacin receptor.

Article Details

Citation

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
DrugTargetPropertyMeasurementpHTemperature (°C)
NiacinHydroxycarboxylic acid receptor 2IC 50 (nM)1407.423Details
NiacinHydroxycarboxylic acid receptor 2EC 50 (nM)10007.423Details