N-(5-chloro-2-(hydroxymethyl)-N-alkyl-arylsulfonamides as gamma-secretase inhibitors

Michael F Parker; Donna M Barten; Carl P Bergstrom; Joanne J Bronson; Jason A Corsa; Milind S Deshpande; Kevin M Felsenstein; Valerie L Guss; Steven B Hansel; Graham Johnson; Daniel J Keavy; Wai Y Lau; Jeremy Mock; C V C Prasad; Craig T Polson; Charles P Sloan; David W Smith; Owen B Wallace; Henry H Wang; Andrew Williams; Ming Zheng

doi:10.1016/j.bmcl.2007.06.022

N-(5-chloro-2-(hydroxymethyl)-N-alkyl-arylsulfonamides as gamma-secretase inhibitors

Bioorg Med Chem Lett. 2007 Aug 15;17(16):4432-6. doi: 10.1016/j.bmcl.2007.06.022. Epub 2007 Jun 10.

Affiliation

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

PMID: 17606371
DOI: 10.1016/j.bmcl.2007.06.022

Abstract

A series of N-alkylbenzenesulfonamides were developed from a high throughput screening hit. Classic and parallel synthesis strategies were employed to produce compounds with good in vitro and in vivo gamma-secretase activity.

MeSH terms

Amyloid Precursor Protein Secretases / antagonists & inhibitors*
Amyloid beta-Peptides / metabolism
Animals
Brain / drug effects
Brain / metabolism
Mice
Mice, Transgenic
Molecular Structure
Protein Binding
Sulfonamides / chemistry*
Sulfonamides / pharmacology*

Substances

Amyloid beta-Peptides
Sulfonamides
Amyloid Precursor Protein Secretases