Design and synthesis of diaminopyrrolidinone inhibitors of human osteoclast cathepsin K.
The structure-based design and synthesis of lactam-constrained azapeptide inhibitors of human cathepsin K are described. Enhanced stability to proteolytic cleavage over acyclic analogues is discussed.
Duffy
K J
KJ
Department of Medicinal Chemistry, SmithKline Beecham Pharmaceuticals, Collegeville, PA 19246, USA.
Ridgers
L H
LH
DesJarlais
R L
RL
Tomaszek
T A
TA
Bossard
M J
MJ
Thompson
S K
SK
Keenan
R M
RM
Veber
D F
DF
D000588:Amines / Q000737:chemistry; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018360:Crystallography, X-Ray; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D010010:Osteoclasts / Q000201:enzymology*; D010455:Peptides / Q000737:chemistry; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000588:Amines; D015853:Cysteine Proteinase Inhibitors; D010455:Peptides; D011760:Pyrrolidinones; C121283:diaminopyrrolidinone; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K