Discovery of a Potent Free Fatty Acid 1 Receptor Agonist with Low Lipophilicity, Low Polar Surface Area, and Robust in Vivo Efficacy
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- 作者：Steffen V. F. Hansen ; Elisabeth Christiansen ; Christian Urban ; Brian D. Hudson ; Claire J. Stocker ; Maria E. Due-Hansen ; Ed T. Wargent ; Bharat Shimpukade ; Reinaldo Almeida ; Christer S. Ejsing ; Michael A. Cawthorne ; Matthias U. Kassack ; Graeme Milligan ; Trond Ulven
- 刊名：Journal of Medicinal Chemistry
- 出版年：2016
- 出版时间：March 24, 2016
- 年：2016
- 卷：59
- 期：6
- 页码：2841-2846
- 全文大小：459K
- ISSN：1520-4804
文摘
The free fatty acid receptor 1 (FFA1 or GPR40) is established as an interesting potential target for treatment of type 2 diabetes. However, to obtain optimal ligands, it may be necessary to limit both lipophilicity and polar surface area, translating to a need for small compounds. We here describe the identification of 24, a potent FFA1 agonist with low lipophilicity and very high ligand efficiency that exhibit robust glucose lowering effect.