3-Substituted gem-cyclohexane sulfone based gamma-secretase inhibitors for Alzheimer's disease: conformational analysis and biological activity

Richard A Jelley; Jason Elliott; Karl R Gibson; Timothy Harrison; Dirk Beher; Earl E Clarke; Huw D Lewis; Mark Shearman; Jonathan D J Wrigley

doi:10.1016/j.bmcl.2006.04.019

3-Substituted gem-cyclohexane sulfone based gamma-secretase inhibitors for Alzheimer's disease: conformational analysis and biological activity

Bioorg Med Chem Lett. 2006 Jul 15;16(14):3839-42. doi: 10.1016/j.bmcl.2006.04.019. Epub 2006 May 6.

Authors

Richard A Jelley¹, Jason Elliott, Karl R Gibson, Timothy Harrison, Dirk Beher, Earl E Clarke, Huw D Lewis, Mark Shearman, Jonathan D J Wrigley

Affiliation

¹ Department of Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK. richard_jelly@yahoo.co.uk

PMID: 16682202
DOI: 10.1016/j.bmcl.2006.04.019

Abstract

Previously, chemistry effort on the gem-cyclohexane series of gamma-secretase inhibitors has focused on the 4-position of the cyclohexane ring. Recently chemistry has been directed towards the 3-position and substitution here has also provided compounds with high gamma-secretase activity.

MeSH terms

Alzheimer Disease / drug therapy
Alzheimer Disease / enzymology
Alzheimer Disease / pathology*
Amyloid Precursor Protein Secretases
Aspartic Acid Endopeptidases
Cyclohexanes / chemistry*
Cyclohexanes / pharmacology
Endopeptidases / metabolism*
Humans
Inhibitory Concentration 50
Models, Chemical
Protease Inhibitors / chemistry*
Protease Inhibitors / pharmacology
Stereoisomerism
Sulfones / chemistry*
Sulfones / pharmacology

Substances

Cyclohexanes
Protease Inhibitors
Sulfones
Amyloid Precursor Protein Secretases
Endopeptidases
Aspartic Acid Endopeptidases
BACE1 protein, human