Humphries Paul S, Bailey Simon, Almaden Jonathon V, Barnum Sandra J, Carlson Thomas J, Christie Lance C, Do Quyen-Quyen T, Fraser James D, Hess Mary, Kellum Jack, Kim Young H, McClellan Guy A, Ogilvie Kathleen M, Simmons Brett H, Skalitzky Donald, Sun Shaoxian, Wilhite David, Zehnder Luke R
Department of Diabetes Chemistry, Pfizer Global R&D, 10770 Science Center Drive, San Diego, CA 92121, USA.
Bioorg Med Chem Lett. 2006 Dec 1;16(23):6120-3. doi: 10.1016/j.bmcl.2006.08.110. Epub 2006 Sep 14.
A series of novel pyridine-3-propanoic acids was synthesized. A structure-activity relationship study of these compounds led to the identification of potent dual PPARalpha/gamma agonists with varied isoform selectivity. Based on the results of efficacy studies in diabetic (db/db) mice, and the desired pharmacokinetic parameters, compounds (S)-14 and (S)-19 were selected for further profiling.
合成了一系列新型吡啶-3-丙酸。对这些化合物的构效关系研究导致鉴定出具有不同亚型选择性的强效双PPARα/γ激动剂。基于在糖尿病（db/db）小鼠中的功效研究结果以及所需的药代动力学参数，选择化合物（S）-14和（S）-19进行进一步分析。
