1. Structure-activity relationship studies of tetrahydroquinolone derivatives as GPR41 modulators.
- Author
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Inuki S, Miyamoto J, Hashimoto N, Shimizu H, Tabuchi H, Kawai A, Greiner LC, Kimura I, and Ohno H
- Subjects
- Structure-Activity Relationship, Humans, Molecular Structure, Quinolones chemistry, Quinolones pharmacology, Quinolones chemical synthesis, Dose-Response Relationship, Drug, Receptors, Cell Surface, Receptors, G-Protein-Coupled metabolism, Receptors, G-Protein-Coupled agonists
- Abstract
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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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