1. Structure-activity relationship studies of tetrahydroquinolone derivatives as GPR41 modulators.
- Author
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Inuki, Shinsuke, Miyamoto, Junki, Hashimoto, Naoki, Shimizu, Hidenori, Tabuchi, Hitomi, Kawai, Atsuko, Greiner, Luca C., Kimura, Ikuo, and Ohno, Hiroaki
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STRUCTURE-activity relationships , *BENZENE derivatives , *SHORT-chain fatty acids , *ARYL group , *G protein coupled receptors - Abstract
[Display omitted] GPR41, a G protein-coupled receptor, serves as a sensor for short-chain fatty acids and plays a crucial role in regulating multiple physiological processes such as the maintenance of metabolic and immune homeostasis. Therefore, the modulation of GPR41 has garnered attention as a potential strategy for the treatment of various disorders. We conducted a structure–activity relationship study on a lead tetrahydroquinolone derivative bearing a 2-(trifluoromethoxy)benzene group that displayed antagonistic activity toward GPR41. Modification of the aryl group attached to the furan moiety revealed that derivatives containing di- or trifluorobenzene, instead of 2-(trifluoromethoxy)benzene, exhibited agonistic activity toward GPR41, comparable with the reported agonistic modulator AR420626. These results suggest that the aryl group plays a pivotal role in regulating the activity of compounds toward GPR41, providing valuable insights for the design of GPR41 modulators. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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