Discovery and parallel synthesis of a new class of cathepsin K inhibitors.
Peptidomimetic aminomethyl ketones have been identified as a new class of cathepsin K inhibitors. Traditional and high-speed parallel synthesis techniques were applied to investigate this series. Structure-activity relationships were established, and certain analogues were characterized with IC(50) values in the range 200-500 nM.
Smith
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RA
Department of Chemistry Research, Bayer Research Center, 400 Morgan Lane, West Haven, CT 06516, USA. roger.smith.b@bayer.com
Bhargava
A
A
Browe
C
C
Chen
J
J
Dumas
J
J
Hatoum-Mokdad
H
H
Romero
R
R
D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D020128:Inhibitory Concentration 50; D007659:Ketones / Q000737:chemistry*; D007700:Kinetics; D018716:Molecular Mimicry; D013329:Structure-Activity Relationship
D015853:Cysteine Proteinase Inhibitors; D007659:Ketones; D002403:Cathepsins; D056657:Cathepsin K