Solid phase synthesis and SAR of small molecule agonists for the GPR40 receptor
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- 作者：Stephen C. McKeown ; David F. Corbett ; Aaron S. Goetz ; Thomas R. Littleton ; Eric Bigham ; Celia P. Briscoe ; Andrew J. Peat ; Steve P Watson ; Deirdre M.B. Hickey
- 关键词：GPR40 agonist ; Diabetes ; Solid phase chemistry
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2007
- 出版时间：15 March 2007
- 年：2007
- 卷：17
- 期：6
- 页码：1584-1589
- 全文大小：177 K
文摘
The discovery, synthesis and structure–activity relationship (SAR) of novel carboxylic acid agonists for GPR40 are described. Aryl propionic acid 1, identified from a high throughput screen, was selected for chemical exploration. Compound 2 was identified as our lead molecule through efficient solid phase combinatorial array chemistry and had an attractive in vitro and in vivo pharmacokinetic profile in rat. These ligands may prove useful in establishing a role for GPR40 in insulin regulation.