2. Academic Validation
  3. Discovery and SAR studies of a novel series of noncovalent cathepsin S inhibitors

Discovery and SAR studies of a novel series of noncovalent cathepsin S inhibitors

  • Bioorg Med Chem Lett. 2005 Mar 15;15(6):1687-91. doi: 10.1016/j.bmcl.2005.01.045.
Darin J Gustin 1,  Clark A Sehon,  Jianmei Wei,  Hui Cai,  Steven P Meduna,  Haripada Khatuya,  Siquan Sun,  Yin Gu,  Wen Jiang,  Robin L Thurmond,  Lars Karlsson,  James P Edwards
Affiliations

Affiliation

  • 1 Johnson and Johnson Pharmaceutical Research and Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, USA.
PMID: 15745822 DOI: 10.1016/j.bmcl.2005.01.045
Abstract

A novel series of competitive, reversible Cathepsin S (CatS) inhibitors was discovered and optimized. The 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety was found to be an effective replacement for the 4-arylpiperazin-1-yl group found in our earlier series of CatS inhibitors. This replacement imparted improved PK properties as well as decreased off-target activity. Optimization of the ketobenzimidazole moiety led to the discovery of the lead compound JNJ 10329670, which represents a novel class of selective, noncovalent, reversible, and orally bioavailable inhibitors of Cathepsin S.

Figures