(4-Piperidinylphenyl)aminoethyl amides as a novel class of non-covalent cathepsin K inhibitors

Tae-Seong Kim; Andrew B Hague; Tony I Lee; Brian Lian; Christopher M Tegley; Xianghong Wang; Teresa L Burgess; Yi-Xin Qian; Sandra Ross; Philip Tagari; Chi-Hwei Lin; Carol Mayeda; Jennifer Dao; Steven Jordan; Christopher Mohr; Janet Cheetham; Vellarkad Viswanadhan; Andrew S Tasker

doi:10.1016/j.bmcl.2003.10.009

(4-Piperidinylphenyl)aminoethyl amides as a novel class of non-covalent cathepsin K inhibitors

Bioorg Med Chem Lett. 2004 Jan 5;14(1):87-90. doi: 10.1016/j.bmcl.2003.10.009.

Authors

Tae-Seong Kim¹, Andrew B Hague, Tony I Lee, Brian Lian, Christopher M Tegley, Xianghong Wang, Teresa L Burgess, Yi-Xin Qian, Sandra Ross, Philip Tagari, Chi-Hwei Lin, Carol Mayeda, Jennifer Dao, Steven Jordan, Christopher Mohr, Janet Cheetham, Vellarkad Viswanadhan, Andrew S Tasker

Affiliation

¹ Department of Chemistry Research and Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. [email protected]

PMID: 14684304
DOI: 10.1016/j.bmcl.2003.10.009

Abstract

A series of (4-piperidinylphenyl)aminoethyl amides based on dipeptide anilines were synthesized and tested against cathepsin K, cathepsin L and cathepsin B. These new non-covalent inhibitors exhibited single-digit nM inhibition of the cysteine proteases. Compounds 3 and 7 demonstrated potency in both mouse and human osteoclast resorption assays.

MeSH terms

Amides / chemistry*
Amides / pharmacology
Amides / therapeutic use
Animals
Bone Resorption / drug therapy
Bone Resorption / enzymology
Cathepsin K
Cathepsins / antagonists & inhibitors*
Cathepsins / metabolism
Cysteine Proteinase Inhibitors / chemistry*
Cysteine Proteinase Inhibitors / pharmacology
Cysteine Proteinase Inhibitors / therapeutic use
Humans
Mice
Piperidines / chemistry*
Piperidines / pharmacology
Piperidines / therapeutic use

Substances

Amides
Cysteine Proteinase Inhibitors
Piperidines
Cathepsins
CTSK protein, human
Cathepsin K
Ctsk protein, mouse