Discovery of 2,4,6-trisubstituted N-arylsulfonyl piperidines as gamma-secretase inhibitors

Hongmei Li; Theodros Asberom; Thomas A Bara; John W Clader; William J Greenlee; Hubert B Josien; Mark D McBriar; Amin Nomeir; Dmitri A Pissarnitski; Murali Rajagopalan; Ruo Xu; Zhiqiang Zhao; Lixin Song; Lili Zhang

doi:10.1016/j.bmcl.2007.09.006

Discovery of 2,4,6-trisubstituted N-arylsulfonyl piperidines as gamma-secretase inhibitors

Bioorg Med Chem Lett. 2007 Nov 15;17(22):6290-4. doi: 10.1016/j.bmcl.2007.09.006. Epub 2007 Sep 7.

Authors

Hongmei Li¹, Theodros Asberom, Thomas A Bara, John W Clader, William J Greenlee, Hubert B Josien, Mark D McBriar, Amin Nomeir, Dmitri A Pissarnitski, Murali Rajagopalan, Ruo Xu, Zhiqiang Zhao, Lixin Song, Lili Zhang

Affiliation

¹ Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. [email protected]

PMID: 17890085
DOI: 10.1016/j.bmcl.2007.09.006

Abstract

Development of cis-2,4,6-trisubstituted piperidine N-arylsulfonamides as gamma-secretase inhibitors for the potential treatment of Alzheimer's disease (AD) is reported.

MeSH terms

Amyloid Precursor Protein Secretases / antagonists & inhibitors*
Cytochrome P-450 CYP3A / drug effects
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Inhibitory Concentration 50
Molecular Structure
Piperidines / chemical synthesis*
Piperidines / chemistry
Piperidines / pharmacology*
Structure-Activity Relationship
Sulfonamides / chemistry

Substances

Enzyme Inhibitors
Piperidines
Sulfonamides
Cytochrome P-450 CYP3A
CYP3A4 protein, human
Amyloid Precursor Protein Secretases