(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.

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