N-Bridged bicyclic sulfonamides as inhibitors of gamma-secretase

Simeon Bowers; Gary D Probst; Anh P Truong; Roy K Hom; Andrei W Konradi; Hing L Sham; Albert W Garofalo; Karina Wong; Erich Goldbach; Kevin P Quinn; John-Michael Sauer; William Wallace; Lan Nguyen; Susanna S Hemphill; Michael P Bova; Guriqbal S Basi

doi:10.1016/j.bmcl.2009.10.060

N-Bridged bicyclic sulfonamides as inhibitors of gamma-secretase

Bioorg Med Chem Lett. 2009 Dec 15;19(24):6952-6. doi: 10.1016/j.bmcl.2009.10.060. Epub 2009 Oct 30.

Authors

Simeon Bowers¹, Gary D Probst, Anh P Truong, Roy K Hom, Andrei W Konradi, Hing L Sham, Albert W Garofalo, Karina Wong, Erich Goldbach, Kevin P Quinn, John-Michael Sauer, William Wallace, Lan Nguyen, Susanna S Hemphill, Michael P Bova, Guriqbal S Basi

Affiliation

¹ Department of Medicinal Chemistry, Elan Pharmaceuticals, 800 Gateway Boulevard, South San Francisco, CA 94080, USA.

PMID: 19879755
DOI: 10.1016/j.bmcl.2009.10.060

Abstract

The structural modification of a series of [3.3.1] bicyclic sulfonamide based gamma-secretase inhibitors is described. Appropriate substitution on the bicyclic scaffold provides a significant increase in the metabolic stability of the compounds resulting in an improved in vivo metabolic profile.

MeSH terms

Alzheimer Disease / drug therapy
Alzheimer Disease / enzymology*
Amyloid Precursor Protein Secretases / antagonists & inhibitors*
Bridged Bicyclo Compounds / chemistry*
Bridged Bicyclo Compounds / pharmacology
Bridged Bicyclo Compounds / therapeutic use
Humans
Protease Inhibitors / chemistry*
Protease Inhibitors / pharmacology
Protease Inhibitors / therapeutic use
Structure-Activity Relationship
Sulfonamides / chemistry*
Sulfonamides / pharmacology
Sulfonamides / therapeutic use

Substances

Bridged Bicyclo Compounds
Protease Inhibitors
Sulfonamides
Amyloid Precursor Protein Secretases