152801-69-9Relevant academic research and scientific papers
Discovery of a novel oxime ether scaffold as potent and orally bioavailable free fatty acid receptor 1 agonists
Li, Zheng,Yang, Jianyong,Gu, Weijie,Cao, Guoshen,Fu, Xiaoting,Sun, Xuedan,Zhang, Yu,Jin, Hui,Huang, Wenlong,Qian, Hai
, p. 46356 - 46365 (2016)
The free fatty acid receptor 1 (FFA1) plays a key role in amplifying glucose-stimulated insulin secretion in pancreatic β-cells. Most of the reported FFA1 agonists contain a biphenyl scaffold, which is associated with toxicity as verified by Daiichi Sankyo. Herein, we describe the systematic exploration of a non-biphenyl scaffold to improve the druggability of GW9508 (β-oxidation, Fsp3 = 0.13, tPSA = 58.5 ?2) directed by Fsp3 and tPSA values. All these optimizations ultimately led to the identification of compound 21, an unconventional agonist (EC50 = 72.5 nM) bearing a methyl oxime ether scaffold. Moreover, compound 21 revealed improved drug-like properties (Fsp3 = 0.23, tPSA = 86.6 ?2) when compared to GW9508 (Fsp3 = 0.13, tPSA = 58.5 ?2) and an even higher binding efficiency index (BEI = 15.3) than TAK-875 (BEI = 14.3). Further pharmacological studies suggested that compound 21 has a considerable hypoglycemic effect in both normal and type 2 diabetic mice with a low risk of hypoglycemia. In addition, the docking study promoted our understanding of the ligand-binding pocket. This information might help towards the design of more promising new molecular entities.
SUBSTITUTED HETEROCYCLIC DERIVATIVES AS GPR AGONISTS AND USES THEREOF
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Page/Page column 109; 110, (2015/03/16)
The present invention generally relates to substituted heterocyclic derivatives (the compounds of Formula (I)), processes for their preparation, pharmaceutical compositions containing said compounds, their use as G-protein coupled receptor (GPR) agonists, particularly as GPR40 agonists and methods of using these compounds in the treatment of GPR40 mediated diseases or conditions such as Type 2 diabetes, obesity, dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.
ORGANIC PHOSPHORUS COMPOUNDS 105 SYNTHESIS AND PROPERTIES OF 2-AMINO-2-ARYLETHYLPHOSPHONIC ACIDS AND DERIVATIVES
Maier, Ludwig,Diel, Peter J.
, p. 245 - 256 (2007/10/03)
2-Amino-2-arylethylphosphonic acids, 6a to 6q have been prepared from the corresponding 2-acetoxyimino- or 2-methoxyimino-2-aryl-ethylphosphonates, 3 or 4, by hydrogenation using Raney-Ni as a catalyst, followed by hydrolysis with HCl. 3 and 4 were obtain
