结构-活性关系研究与游离脂肪酸受体 2 强力拮抗剂的发现
Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2.
机构信息
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark.
Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, Scotland, UK.
出版信息
ChemMedChem. 2021 Nov 5;16(21):3326-3341. doi: 10.1002/cmdc.202100356. Epub 2021 Sep 12.
Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB (1). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.
游离脂肪酸受体 2（FFA2）是一种短链脂肪酸感应器，已被鉴定为治疗代谢和炎症性疾病的一个有趣的潜在药物靶点。尽管已经有几种配体系列被确定为该受体的配体，但仍然需要改进的化合物。最有效和常用的拮抗剂之一是酰胺取代的苯丁酸，称为 CATPB（1）。我们在此报告对该化合物的结构-活性关系的探索，导致发现了具有更高效力的类似物。优选化合物 37（TUG-1958）不仅效力提高，而且溶解度高，药代动力学性质良好。
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