180716-16-9Relevant academic research and scientific papers
Design and optimization of 2,3-dihydrobenzo[b][1,4]dioxine propanoic acids as novel GPR40 agonists with improved pharmacokinetic and safety profiles
Guo, Bin,Guo, Shimeng,Huang, Jing,Li, Jingya,Li, Jia,Chen, Qian,Zhou, Xianli,Xie, Xin,Yang, Yushe
, p. 5780 - 5791 (2018/11/06)
GPR40 has become a new potential therapeutic target for the treatment of diabetes due to its role in mediating the enhancement of glucose-stimulated insulin secretion in pancreatic β cells with a low risk of hypoglycemia. As an effort to extend the chemical space and identify structurally distinct GPR40 agonists with improved liver safety, a novel series of fused-ring phenyl propanoic acid analogues were designed. Comprehensive structure-activity relationship studies around novel scaffolds were conducted and led to several analogues exhibited potent GPR40 agonistic activities and high selectivity against other fatty acid receptors. Further evaluation of pharmacokinetic (PK) profiles and in vivo efficacy identified compound 40a with excellent PK properties and significant glucose-lowering efficacy during an oral glucose tolerance test. In addition, compound 40a displayed lower hepatobiliary transporter inhibition and favorable druggability. All results indicate that compound 40a is a promising candidate for further development.
BENZENE-FUSED 6-MEMBERED OXYGEN-CONTAINING HETEROCYCLIC DERIVATIVES OF BICYCLIC HETEROARYLS
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Page/Page column 81, (2011/06/23)
The invention relates to new derivatives of formula I, wherein the substituents are as defined in the specification; to processes for the preparation of such derivatives; pharmaceutical compositions comprising such derivatives; such derivatives as a medicament; such derivatives for the treatment of a proliferative disease.
Chroman and benzofuran derivatives as 5-hydroxytryptamine-6 ligands
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, (2008/06/13)
The present invention provides a compound of formula I and the use thereof for the therapeutic treatment of disorders relating to or affected by the 5-HT6 receptor.
New generation dopaminergic agents. 1. Discovery of a novel scaffold which embraces the D2 agonist pharmacophore. Structure-activity relationships of a series of 2-(aminomethyl)chromans
Mewshaw, Richard E.,Kavanagh, Joseph,Stack, Gary,Marquis, Karen L.,Shi, Xiaojie,Kagan, Michael Z.,Webb, Michael B.,Katz, Alan H.,Park, Anna,Kang, Young H.,Abou-Gharbia, Magid,Scerni, Rosemary,Wasik, Theodore,Cortes-Burgos, Luz,Spangler, Taylor,Brennan, Julie A.,Piesla, Michael,Mazandargmi, Hossein,Cockett, Mark I.,Ochalski, Rafal,Coupet, Joseph,Andree, Terrance H.
, p. 4235 - 4256 (2007/10/03)
A series of 2-(aminomethyl)chromans (2-AMCs) was synthesized and evaluated for their affinity and selectivity for both the high- and low- affinity agonist states (D2(High) and D2(Low), respectively) of the dopamine (DA) D2
