Nongenomic Actions of Bile Acids. Synthesis and Preliminary Characterization of 23- and 6,23-Alkyl-Substituted Bile Acid Derivatives as Selective Modulators for the G-Protein Coupled Receptor TGR5
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- 作者：Roberto Pellicciari ; Hiroyuki Sato ; Antimo Gioiello ; Gabriele Costantino ; Antonio Macchiarulo ; Bahman M. Sadeghpour ; Gianluca Giorgi ; Kristina Schoonjans ; Johan Auwerx
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：September 6, 2007
- 年：2007
- 卷：50
- 期：18
- 页码：4265 - 4268
- 全文大小：135K
- 年卷期：v.50,no.18(September 6, 2007)
- ISSN：1520-4804
文摘
23-Alkyl-substituted and 6,23-alkyl-disubstituted derivativesof chenodeoxycholic acid are identified as potent and selective agonistsof TGR5, a G-protein coupled receptor for bile acids (BAs). Inparticular, we show that methylation at the C-23(S) position of naturalBAs confers a marked selectivity for TGR5 over FXR, while the 6
-alkyl substitution increases the potency at both receptors. The presentresults allow for the first time a pharmacological differentiation ofgenomic versus nongenomic effects mediated by BA derivatives.
-alkyl substitution increases the potency at both receptors. The presentresults allow for the first time a pharmacological differentiation ofgenomic versus nongenomic effects mediated by BA derivatives.