Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonists: Mesylpropoxy Appendage Lowers Lipophilicity and Improves ADME Properties
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- 作者：Elisabeth Christiansen ; Maria E. Due-Hansen ; Christian Urban ; Manuel Grundmann ; Ralf Schr枚der ; Brian D. Hudson ; Graeme Milligan ; Michael A. Cawthorne ; Evi Kostenis ; Matthias U. Kassack ; Trond Ulven
- 刊名：Journal of Medicinal Chemistry
- 出版年：2012
- 出版时间：July 26, 2012
- 年：2012
- 卷：55
- 期：14
- 页码：6624-6628
- 全文大小：270K
- 年卷期：v.55,no.14(July 26, 2012)
- ISSN：1520-4804
文摘
FFA1 (GPR40) is a new target for treatment of type 2 diabetes. We recently identified the potent FFA1 agonist TUG-469 (5). Inspired by the structurally related TAK-875, we explored the effects of a mesylpropoxy appendage on 5. The appendage significantly lowers lipophilicity and improves metabolic stability while preserving potency, resulting in discovery of the potent FFA1 agonist 13.