Discovery of selective and nonpeptidic cathepsin S inhibitors.

Basic Information

ID: ALA1155066

Journal: Bioorg Med Chem Lett

Title: Discovery of selective and nonpeptidic cathepsin S inhibitors.

Authors: Irie O, Ehara T, Iwasaki A, Yokokawa F, Sakaki J, Hirao H, Kanazawa T, Teno N, Horiuchi M, Umemura I, Gunji H, Masuya K, Hitomi Y, Iwasaki G, Nonomura K, Tanabe K, Fukaya H, Kosaka T, Snell CR, Hallett A.

Abstract: Nonpeptidic, selective, and potent cathepsin S inhibitors were derived from an in-house pyrrolopyrimidine cathepsin K inhibitor by modification of the P2 and P3 moieties. The pyrrolopyrimidine-based inhibitors show nanomolar inhibition of cathepsin S with over 100-fold selectivity against other cysteine proteases, including cathepsin K and L. Some of the inhibitors showed cellular activities in mouse splenocytes as well as oral bioavailabilities in rats.

CiteXplore: 18572405

DOI: 10.1016/j.bmcl.2008.06.009

Patent ID: