Discovery of Biaryl Anthranilides as Full Agonists for the High Affinity Niacin Receptor
详细信息 查看全文
- 作者：Hong C. Shen ; Fa-Xiang Ding ; Silvi Luell ; Michael J. Forrest ; Ester Carballo-Jane ; Kenneth K. Wu ; Tsuei-Ju Wu ; Kang Cheng ; Larissa C. Wilsie ; Mihajlo L. Krsmanovic ; Andrew K. Taggart ; Ning Ren ; Tian-Q
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：December 13, 2007
- 年：2007
- 卷：50
- 期：25
- 页码：6303 - 6306
- 全文大小：121K
- 年卷期：v.50,no.25(December 13, 2007)
- ISSN：1520-4804
文摘
Biaryl anthranilides are reported as potent and selective full agonists for the high affinity niacin receptor GPR109A. The SAR presented outlines approaches to reduce serum shift and both CYPCYP2C8 and CYP2C9 liabilities, while improving PK and maintaining excellent receptor activity. Compound 2i exhibited good in vivo antilipolytic efficacy while providing a significantly improved therapeutic index over vasodilation (flushing) with respect to niacin in the mouse model.