1.
Bioorg Med Chem Lett
; 18(14): 3988-91, 2008 Jul 15.
Artículo
en Inglés
| MEDLINE
| ID: mdl-18571402
RESUMEN
Cathepsin K is the key regulator in the osteoclast-mediated bone resorption. Here, we found the correlation between the inhibitory activities of carbonitrile derivatives in the enzymatic activity of cathepsin K and their binding scores predicted using FlexX-Pharm docking program. The binding pattern of [1-(2-cyano-tetrahydro-pyridazine-1-carbonyl)-2-methy-propyl]-carbamic acid benzyl ester (8), one member of this series, was similar to that of the reference. In a bone pit formation assay, compound 8 was shown to dose-dependently inhibit the bone resorptive activity of mature osteoclasts.