Design, synthesis, and structure-activity relationship studies of N-arylsulfonyl morpholines as γ-secretase inhibitors

Hongmei Li; Ruo Xu; David Cole; John W Clader; William J Greenlee; Amin A Nomeir; Lixin Song; Lili Zhang

doi:10.1016/j.bmcl.2010.09.028

Design, synthesis, and structure-activity relationship studies of N-arylsulfonyl morpholines as γ-secretase inhibitors

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6606-9. doi: 10.1016/j.bmcl.2010.09.028. Epub 2010 Sep 16.

Authors

Hongmei Li¹, Ruo Xu, David Cole, John W Clader, William J Greenlee, Amin A Nomeir, Lixin Song, Lili Zhang

Affiliation

¹ Department of Chemical Research, Merck Research Lab., 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. hongmei.li@spcorp.com

PMID: 20933414
DOI: 10.1016/j.bmcl.2010.09.028

Abstract

Design and synthesis of cis-2,6-disubstituted N-arylsulfonyl morpholines as novel γ-secretase inhibitors for the potential treatment of Alzheimer's disease (AD) is reported. Several different small alkyl groups are installed on the left-hand side to lower the CYP3A4 liability while maintaining excellent in vitro potency.

MeSH terms

Amyloid Precursor Protein Secretases / antagonists & inhibitors*
Drug Design
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Morpholines / chemical synthesis*
Morpholines / chemistry
Morpholines / pharmacology*
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Morpholines
Amyloid Precursor Protein Secretases