5-Aminopyrimidin-2-ylnitriles as cathepsin K inhibitors

Andrew D Morley; Peter W Kenny; Brenda Burton; Robert A Heald; Philip A Macfaul; Julia Mullett; Ken Page; Soraya S Porres; Lyn Rosenbrier Ribeiro; Phil Smith; Stuart Ward; Tina J Wilkinson

doi:10.1016/j.bmcl.2009.01.110

5-Aminopyrimidin-2-ylnitriles as cathepsin K inhibitors

Bioorg Med Chem Lett. 2009 Mar 15;19(6):1658-61. doi: 10.1016/j.bmcl.2009.01.110. Epub 2009 Feb 6.

Authors

Andrew D Morley¹, Peter W Kenny, Brenda Burton, Robert A Heald, Philip A Macfaul, Julia Mullett, Ken Page, Soraya S Porres, Lyn Rosenbrier Ribeiro, Phil Smith, Stuart Ward, Tina J Wilkinson

Affiliation

¹ AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.

PMID: 19231183
DOI: 10.1016/j.bmcl.2009.01.110

Abstract

A series of pyrimidine nitrile inhibitors of Cathepsin K with reduced glutathione reactivity has been identified and Molecular Core Matching (MoCoM) has been used to quantify the effect of an amino substituent at C5.

MeSH terms

Cathepsin K
Cathepsins / antagonists & inhibitors*
Cathepsins / chemistry
Chemistry, Pharmaceutical / methods
Cysteine Proteinase Inhibitors / chemical synthesis*
Cysteine Proteinase Inhibitors / pharmacology
Drug Design
Humans
Lysosomes / enzymology
Models, Chemical
Molecular Structure
Nitriles / chemical synthesis*
Osteoarthritis / drug therapy
Osteoclasts
Osteoporosis / drug therapy
Pyrimidines / chemistry
Structure-Activity Relationship
Technology, Pharmaceutical / methods

Substances

Cysteine Proteinase Inhibitors
Nitriles
Pyrimidines
Cathepsins
CTSK protein, human
Cathepsin K