Title of article :
Potent and selective P2–P3 ketoamide inhibitors of cathepsin K with good pharmacokinetic properties via favorable P1′, P1, and/or P3 substitutions
Author/Authors :
David G. Barrett، نويسنده , , John G. Catalano، نويسنده , , David N. Deaton، نويسنده , , Anne M. Hassell، نويسنده , , Stacey T. Long، نويسنده , , Aaron B. Miller، نويسنده , , Larry R. Miller، نويسنده , , Lisa M. Shewchuk، نويسنده , , Kevin J. Wells-Knecht، نويسنده , , Derril H. Willard Jr.، نويسنده , , Lois L. Wright، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2004
Abstract :
A series of ketoamides were synthesized and evaluated for inhibitory activity against cathepsin K. Exploration of the interactions between achiral P2 substituents and the cysteine protease based on molecular modelling suggestions resulted in potent cathepsin K inhibitors that demonstrated high selectivity versus cathepsins B, H, and L. Subsequent modifications of the P3, P1, and P1′ moieties afforded orally bioavailable inhibitors.
Keywords :
Cathepsin K , Ketoamide , Cysteine protease inhibitor.* Corresponding author. Tel.: +1-919-483-6264 , fax: +1-919-483-6053 , e-mail: john.g.catalano@gsk.com
Journal title :
Bioorganic & Medicinal Chemistry Letters
Journal title :
Bioorganic & Medicinal Chemistry Letters
