Fluorinated pyrazole acids are agonists of the high affinity niacin receptor GPR109a
- 作者：Philip J. Skinner ; Martin C. Cherrier ; Peter J. Webb ; Young-Jun Shin ; Tawfik Gharbaoui ; Andrew Lindstrom ; Vu Hong ; Susan Y. Tamura ; Huong T. Dang ; Cameron C. Pride ; Ruoping Chen ; Jeremy G. Richman ; Da
- 关键词：Niacin ; GPR109a ; GPR109b ; GPCRs ; Lipolysis ; Free fatty acids ; Selectfluor ; Cutaneous flushing ; Pyrazole carboxylic acids ; HM74 ; HM74a ; PUMA-G
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2007
- 期刊代码：10_0960894x
- 类别：ch
- 出版时间：15 October 2007
- 卷：17
- 期：20
- 页码：5620-5623
- 文件大小：290 K
摘要
A series of 5-alkyl pyrazole-3-carboxylic acids were prepared and found to act as potent and selective agonists of the human GPCR, GPR109a, the high affinity nicotinic acid receptor. No activity was observed at the highly homologous low affinity niacin receptor, GPR109b. A further series of 4-fluoro-5-alkyl pyrazole-3-carboxylic acids were shown to display similar potency. One example from the series was shown to have improved properties in vivo compared to niacin.