4-Aminophenoxyacetic acids as a novel class of reversible cathepsin K inhibitors

Tsuyoshi Shinozuka; Kousei Shimada; Satoshi Matsui; Takahiro Yamane; Mayumi Ama; Takeshi Fukuda; Motohiko Taki; Satoru Naito

doi:10.1016/j.bmcl.2005.12.053

4-Aminophenoxyacetic acids as a novel class of reversible cathepsin K inhibitors

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1502-5. doi: 10.1016/j.bmcl.2005.12.053. Epub 2005 Dec 27.

Authors

Tsuyoshi Shinozuka¹, Kousei Shimada, Satoshi Matsui, Takahiro Yamane, Mayumi Ama, Takeshi Fukuda, Motohiko Taki, Satoru Naito

Affiliation

¹ Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. sinozu@sankyo.co.jp

PMID: 16380250
DOI: 10.1016/j.bmcl.2005.12.053

Abstract

We have designed and synthesized a novel series of 3-biphenylamino acid amides as cathepsin K inhibitors based on compound I. In these inhibitors, we have discovered 4-aminophenoxyacetic acids 43 and 47 with good IC(50) values, although lipophilic groups are favorable for the hydrophobic S1' pocket.

MeSH terms

Cathepsin K
Cathepsins / antagonists & inhibitors*
Cathepsins / metabolism
Cysteine Proteinase Inhibitors / chemical synthesis*
Cysteine Proteinase Inhibitors / pharmacology
Humans
Phenoxyacetates / chemical synthesis*
Phenoxyacetates / pharmacology
Recombinant Proteins / antagonists & inhibitors
Recombinant Proteins / metabolism
Structure-Activity Relationship

Substances

Cysteine Proteinase Inhibitors
Phenoxyacetates
Recombinant Proteins
Cathepsins
CTSK protein, human
Cathepsin K