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Bioorg Med Chem Lett
; 15(15): 3540-6, 2005 Aug 01.
Article
in English
| MEDLINE
| ID: mdl-15982880
ABSTRACT
An orally bioavailable series of ketoamide-based cathepsin K inhibitors with good pharmacokinetic properties has been identified. Starting from a potent inhibitor endowed with poor drug properties, conformational constraint of the P(2)-P(3) linker and modifications to P(1') elements led to an enhancement in potency, solubility, clearance, and bioavailability. These optimized inhibitors attenuated bone resorption in a rat TPTX hypocalcemic bone resorption model.