Iminoheterocycles as gamma-secretase modulators

  • Bioorg Med Chem Lett. 2010 Sep 15;20(18):5380-4. doi: 10.1016/j.bmcl.2010.07.121.
John P Caldwell  1 ,  Chad E Bennett ,  Troy M McCracken ,  Robert D Mazzola ,  Thomas Bara ,  Alexei Buevich ,  Duane A Burnett ,  Inhou Chu ,  Mary Cohen-Williams ,  Hubert Josein ,  Lynn Hyde ,  Julie Lee ,  Brian McKittrick ,  Lixin Song ,  Giuseppe Terracina ,  Johannes Voigt ,  Lili Zhang ,  Zhaoning Zhu
Affiliations
  • 1. Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States. [email protected]
PMID: 20724152 DOI: 10.1016/j.bmcl.2010.07.121
Abstract

The synthesis of a novel series of iminoheterocycles and their structure-activity relationship (SAR) as modulators of gamma-secretase activity will be detailed. Encouraging SAR generated from a monocyclic core led to a structurally unique bicyclic core. Selected compounds exhibit good potency as gamma-secretase modulators, excellent rat pharmacokinetics, and lowering of Abeta42 levels in various in vivo models.