Sar Studies on Fxr Modulators Led to the Discovery of the First Combined Fxr Antagonistic/Tgr5 Agonistic Compound
- 29 January 2016
- journal article
- Published by Taylor & Francis in Future Medicinal Chemistry
- Vol. 8 (2) , 133-148
Abstract
Background: Bile acids can serve as signaling molecules by activating the nuclear receptor FXR and the G-protein-coupled receptor TGR5 and both bile acid receptors are prominent experimental drug targets. Results/methodology: In this study we optimized the fatty acid mimetic compound pirinixic acid to a new scaffold with the aim to develop novel FXR modulatory compounds. After a multistep structure–activity optimization process, we discovered FXR agonistic compounds and the first dual FXR antagonistic and TGR5 agonistic compound 79a. Conclusion: With this novel dual activity profile on both bile acid receptors 79a might be a valuable pharmalogical tool to further study the bile acid signaling network.Keywords
Funding Information
- Else Kröner-Fresenius Foundation
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