Synthesis, SAR, and evaluation of aryl triazoles as novel gamma secretase modulators (GSMs) are presented in this communication. Starting from the literature and in-house leads, we evaluated a range of five-membered heterocycles as replacements for olefins commonly found in non-acid GSMs. 1,2,3-C-aryl-triazoles were identified as suitable replacements which exhibited good modulation of gamma-secretase activity, excellent pharmacokinetics and good central lowering of A beta 42 in Sprague-Dawley rats.
Bioorganic & medicinal chemistry letters 07/2011; 21(13):4083-7. DOI:10.1016/j.bmcl.2011.04.089 · 2.65 Impact Factor