960605-16-7Relevant academic research and scientific papers
Affinity and kinetics study of anthranilic acids as HCA2 receptor agonists
Van Veldhoven, Jacobus P.D.,Liu, Rongfang,Thee, Stephanie A.,Wouters, Yessica,Verhoork, Sanne J.M.,Mooiman, Christiaan,Louvel, Julien,Ijzerman, Adriaan P.
, p. 4013 - 4025 (2015/03/04)
Structure-affinity relationship (SAR) and structure-kinetics relationship (SKR) studies were combined to investigate a series of biphenyl anthranilic acid agonists for the HCA2 receptor. In total, 27 compounds were synthesized and twelve of them showed higher affinity than nicotinic acid. Two compounds, 6g (IC50 = 75 nM) and 6z (IC50 = 108 nM) showed a longer residence time profile compared to nicotinic acid, exemplified by their kinetic rate index (KRI) values of 1.31 and 1.23, respectively. The SAR study resulted in the novel 2-F, 4-OH derivative (6x) with an IC50 value of 23 nM as the highest affinity HCA2 agonist of the biphenyl series, although it showed a similar residence time as nicotinic acid. The SAR and SKR data suggest that an early compound selection based on binding kinetics is a promising addition to the lead optimization process.
Discovery of biaryl anthranilides as full agonists for the high affinity niacin receptor
Shen, Hong C.,Ding, Fa-Xiang,Luell, Silvi,Forrest, Michael J.,Carballo-Jane, Ester,Wu, Kenneth K.,Wu, Tsuei-Ju,Cheng, Kang,Wilsie, Larissa C.,Krsmanovic, Mihajlo L.,Taggart, Andrew K.,Ren, Ning,Cai, Tian-Quan,Deng, Qiaolin,Chen, Qing,Wang, Junying,Wolff, Michael S.,Tong, Xinchun,Holt, Tom G.,Waters, M. Gerard,Hammond, Milton L.,Tata, James R.,Colletti, Steven L.
, p. 6303 - 6306 (2008/04/12)
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 maintainin
