Discovery of AMG 369, a Thiazolo[5,4-<i>b</i>]pyridine Agonist of S1P<sub>1</sub> and S1P<sub>5</sub>
Victor J. Cee(Amgen (United States)), Mike Frohn(Amgen (United States)), Brian A. Lanman(Amgen (United States)), Jennifer E. Golden(Amgen (United States)), Kristine Muller(Amgen (United States)), Susana Neira(Amgen (United States)), Alex Pickrell(Amgen (United States)), Heather A. Arnett(Amgen (United States)), Janet Buys(Amgen (United States)), Anu Gore(Amgen (United States)), Mike Fiorino(Amgen (United States)), Michelle Horner(Amgen (United States)), Andrea Itano(Amgen (United States)), Matt R. Lee(Amgen (United States)), Michele McElvain(Amgen (United States)), Scot Middleton(Amgen (United States)), Michael Schrag(Amgen (United States)), Dalia Rivenzon‐Segal(Epix Pharmaceuticals (United States)), Hugo M. Vargas(Amgen (United States)), Han Xu(Amgen (United States)), Yang Xu(Amgen (United States)), Xuxia Zhang(Amgen (United States)), Jerry Siu(Amgen (United States)), Min Wong(Amgen (United States)), Roland W. Bürli(Amgen (United States))
Cited by 54Open Access
Abstract
The optimization of a series of thiazolopyridine S1P1 agonists with limited activity at the S1P3 receptor is reported. These efforts resulted in the discovery of 1-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo-[5,4-b]pyridin-2-yl)benzyl)azetidine-3-carboxylic acid (5d, AMG 369), a potent dual S1P1/S1P5 agonist with limited activity at S1P3 and no activity at S1P2/S1P4. Dosed orally at 0.1 mg/kg, 5d is shown to reduce blood lymphocyte counts 24 h postdose and delay the onset and reduce the severity of experimental autoimmune encephalomyelitis in rat.
Related Papers
No related papers found
Powered by citation graph analysis