Arylaminoethyl carbamates as a novel series of potent and selective cathepsin S inhibitors.
We report a novel series of noncovalent inhibitors of cathepsin S. The synthesis of the peptidomimetic scaffold is described and structure-activity relationships of P3, P1, and P1' subunits are discussed. Lead optimization to a non-peptidic scaffold has resulted in a new class of potent, highly selective, and orally bioavailable cathepsin S inhibitors.
Tully
David C
DC
Genomics Institute of the Novartis Research Foundation, 10675 John J. Hopkins Dr., San Diego, CA 92121, USA. dtully@gnf.org
Liu
Hong
H
Chatterjee
Arnab K
AK
Alper
Phil B
PB
Williams
Jennifer A
JA
Roberts
Michael J
MJ
Mutnick
Daniel
D
Woodmansee
David H
DH
Hollenbeck
Thomas
T
Gordon
Perry
P
Chang
Jonathan
J
Tuntland
Tove
T
Tumanut
Christine
C
Li
Jun
J
Harris
Jennifer L
JL
Karanewsky
Donald S
DS
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002219:Carbamates / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D002219:Carbamates; D009842:Oligopeptides; D011480:Protease Inhibitors; D002403:Cathepsins; C028217:cathepsin S