Design and synthesis of diaminopyrrolidinone inhibitors of human osteoclast cathepsin K

K J Duffy; L H Ridgers; R L DesJarlais; T A Tomaszek; M J Bossard; S K Thompson; R M Keenan; D F Veber

doi:10.1016/s0960-894x(99)00322-4

Design and synthesis of diaminopyrrolidinone inhibitors of human osteoclast cathepsin K

Bioorg Med Chem Lett. 1999 Jul 19;9(14):1907-10. doi: 10.1016/s0960-894x(99)00322-4.

Authors

K J Duffy¹, L H Ridgers, R L DesJarlais, T A Tomaszek, M J Bossard, S K Thompson, R M Keenan, D F Veber

Affiliation

¹ Department of Medicinal Chemistry, SmithKline Beecham Pharmaceuticals, Collegeville, PA 19246, USA.

PMID: 10450951
DOI: 10.1016/s0960-894x(99)00322-4

Abstract

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.

MeSH terms

Amines / chemistry
Cathepsin K
Cathepsins / antagonists & inhibitors*
Cathepsins / metabolism
Crystallography, X-Ray
Cysteine Proteinase Inhibitors / chemical synthesis*
Cysteine Proteinase Inhibitors / metabolism
Cysteine Proteinase Inhibitors / pharmacology*
Drug Design
Humans
Models, Molecular
Osteoclasts / enzymology*
Peptides / chemistry
Pyrrolidinones / chemical synthesis*
Pyrrolidinones / metabolism
Pyrrolidinones / pharmacology
Structure-Activity Relationship

Substances

Amines
Cysteine Proteinase Inhibitors
Peptides
Pyrrolidinones
diaminopyrrolidinone
Cathepsins
CTSK protein, human
Cathepsin K