Carbamate-appended N-alkylsulfonamides as inhibitors of gamma-secretase

Carl P Bergstrom; Charles P Sloan; Wai-Yu Lau; David W Smith; Ming Zheng; Steven B Hansel; Craig T Polson; Jason A Corsa; Donna M Barten; Kevin M Felsenstein; Susan B Roberts

doi:10.1016/j.bmcl.2007.11.102

Carbamate-appended N-alkylsulfonamides as inhibitors of gamma-secretase

Bioorg Med Chem Lett. 2008 Jan 15;18(2):464-8. doi: 10.1016/j.bmcl.2007.11.102. Epub 2007 Dec 3.

Authors

Carl P Bergstrom¹, Charles P Sloan, Wai-Yu Lau, David W Smith, Ming Zheng, Steven B Hansel, Craig T Polson, Jason A Corsa, Donna M Barten, Kevin M Felsenstein, Susan B Roberts

Affiliation

¹ Department of Discovery Chemistry, Research and Development, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA. carl.bergstrom@bms.com

PMID: 18178084
DOI: 10.1016/j.bmcl.2007.11.102

Abstract

The synthesis and gamma-secretase inhibition data for a series of carbamate-appended N-alkylsulfonamides are described. Carbamate 54 was found to significantly reduce brain Abeta in transgenic mice. 54 was also found to possess markedly improved brain levels in transgenic mice compared to previously disclosed 1 and 2.

MeSH terms

Alzheimer Disease / metabolism
Amyloid Precursor Protein Secretases / antagonists & inhibitors*
Amyloid beta-Peptides / antagonists & inhibitors
Amyloid beta-Peptides / metabolism
Animals
Brain / drug effects
Brain / metabolism
Carbamates / chemistry*
Mice
Mice, Transgenic
Protease Inhibitors / chemistry*
Protease Inhibitors / pharmacology*
Structure-Activity Relationship
Sulfonamides / chemistry*
Sulfonamides / pharmacology*

Substances

Amyloid beta-Peptides
Carbamates
Protease Inhibitors
Sulfonamides
Amyloid Precursor Protein Secretases