Exploration of the P1 SAR of aldehyde cathepsin K inhibitors

John G Catalano; David N Deaton; Eric S Furfine; Annie M Hassell; Robert B McFadyen; Aaron B Miller; Larry R Miller; Lisa M Shewchuk; Derril H Willard Jr; Lois L Wright

doi:10.1016/j.bmcl.2003.09.088

Exploration of the P1 SAR of aldehyde cathepsin K inhibitors

Bioorg Med Chem Lett. 2004 Jan 5;14(1):275-8. doi: 10.1016/j.bmcl.2003.09.088.

Authors

John G Catalano¹, David N Deaton, Eric S Furfine, Annie M Hassell, Robert B McFadyen, Aaron B Miller, Larry R Miller, Lisa M Shewchuk, Derril H Willard Jr, Lois L Wright

Affiliation

¹ Department of Medicinal Chemistry, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA.

PMID: 14684342
DOI: 10.1016/j.bmcl.2003.09.088

Abstract

The synthesis and biological activity of a series of aldehyde inhibitors of cathepsin K are reported. Exploration of the properties of the S(1) subsite with a series of alpha-amino aldehyde derivatives substituted at the P(1) position afforded compounds with cathepsin K IC(50)s between 52 microM and 15 nM.

MeSH terms

Aldehydes / chemistry*
Aldehydes / pharmacology
Binding Sites / drug effects
Binding Sites / physiology
Cathepsin K
Cathepsins / antagonists & inhibitors*
Cathepsins / metabolism
Protease Inhibitors / chemistry*
Protease Inhibitors / pharmacology
Structure-Activity Relationship

Substances

Aldehydes
Protease Inhibitors
Cathepsins
Cathepsin K