Synthesis and structure-activity relationship of a novel series of heterocyclic sulfonamide gamma-secretase inhibitors

  • Bioorg Med Chem. 2009 Jul 1;17(13):4708-17. doi: 10.1016/j.bmc.2009.04.052.
Jun Pu  1 ,  Anthony F Kreft ,  Suzan H Aschmies ,  Kevin P Atchison ,  Joshua Berkowitz ,  Thomas J Caggiano ,  Micheal Chlenov ,  George Diamantidis ,  Boyd L Harrison ,  Yun Hu ,  Donna Huryn ,  J Steven Jacobsen ,  Mei Jin ,  Kerri Lipinski ,  Peimin Lu ,  Robert L Martone ,  Koi Morris ,  June Sonnenberg-Reines ,  Dave R Riddell ,  Joan Sabalski ,  Shaiu-Ching Sun ,  Erik Wagner ,  Yiqun Wang ,  Zheng Xu ,  Hua Zhou ,  Lynn Resnick
Affiliations
  • 1. Chemical Sciences, Wyeth Research, Princeton, NJ 08543-8000, USA.
PMID: 19443228 DOI: 10.1016/j.bmc.2009.04.052
Abstract

gamma-Secretase inhibitors have been shown to reduce the production of beta-amyloid, a component of the plaques that are found in brains of patients with Alzheimer's disease. A novel series of heterocyclic sulfonamide gamma-secretase inhibitors that reduce beta-amyloid levels in cells is reported. Several examples of compounds within this series demonstrate a higher propensity to inhibit the processing of amyloid precursor protein compared to Notch, an alternative gamma-secretase substrate.