Optimization of GPR40 Agonists for Type 2 Diabetes
β Scribed by Liu, Jiwen (Jim); Wang, Yingcai; Ma, Zhihua; Schmitt, Mike; Zhu, Liusheng; Brown, Sean P.; Dransfield, Paul J.; Sun, Ying; Sharma, Rajiv; Guo, Qi; Zhuang, Run; Zhang, Jane; Luo, Jian; Tonn, George R.; Wong, Simon; Swaminath, Gayathri; Medina, Julio C.; Lin, Daniel C.-H.; Houze, Jonathan B.
- Book ID
- 125489447
- Publisher
- American Chemical Society
- Year
- 2014
- Tongue
- English
- Weight
- 312 KB
- Volume
- 5
- Category
- Article
- ISSN
- 1948-5875
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Screening of the Merck sample collection identified compound 1 as a weakly potent GPR119 agonist (hEC(50)=3600 nM). Dual termini optimization of 1 led to compound 36 having improved potency, selectivity, and formulation profile, however, modest physical properties (PP) hindered its utility. Design o
## Abstract Dual termini optimization of a bisβpiperidineβbased GPR119 agonist affords an analogue possessing improved potency, selectivity, and formulation profile, but modest physical properties.