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Free fatty acid receptor 1 (FFA1/GPR40) agonists: mesylpropoxy appendage lowers lipophilicity and improves ADME properties. | LitMetric
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Free fatty acid receptor 1 (FFA1/GPR40) agonists: mesylpropoxy appendage lowers lipophilicity and improves ADME properties.

Elisabeth Christiansen Maria E Due-Hansen Christian Urban Manuel Grundmann Ralf Schröder Brian D Hudson Graeme Milligan Michael A Cawthorne Evi Kostenis Matthias U Kassack Trond Ulven

J Med Chem

Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.

Published: July 2012

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.

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http://dx.doi.org/10.1021/jm3002026DOI Listing

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