Exploring bulky natural and natural-like periphery in the design of p-(benzyloxy)phenylpropionic acid agonists of free fatty acid receptor 1 (GPR40)

Sergey O. Kuranov, Olga A. Luzina, Oleksandra Onopchenko, Iryna Pishel, Sergey Zozulya, Maxim Gureev, Nariman F. Salakhutdinov, Mikhail Krasavin

    Результат исследований: Научные публикации в периодических изданияхстатья

    Аннотация

    Six derivatives of 3-phenylpropionic acid bearing various natural and natural-like, spatially defined peripheral motifs have been synthesized and evaluated in vitro for free fatty acid receptor 1 (FFA1) activation. Two frontrunner compounds (bearing a bornyl and cytosine groups) were evaluated in an oral glucose tolerance test in mice where both demonstrated the ability to sustain blood glucose levels following a glucose challenge. The bornyl compound displayed a somewhat superior, dose-dependent efficacy and, therefore, can be regarded as a lead compounds for further development as a therapeutic agent for type 2 diabetes mellitus. Its high affinity to FFA1 was rationalized by docking experiments.

    Язык оригиналаанглийский
    Номер статьи103830
    ЖурналBioorganic Chemistry
    Том99
    DOI
    СостояниеОпубликовано - июн 2020

    Предметные области Scopus

    • Биохимия
    • Молекулярная биология
    • Поиск новых лекарств
    • Органическая химия

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