Difluoroethylamines as an amide isostere in inhibitors of cathepsin K.

Journal Article

The trifluoroethylamine group found in cathepsin K inhibitors like odanacatib can be replaced by a difluoroethylamine group. This change increased the basicity of the nitrogen which positively impacted the log D. This translated into an improved oral bioavailability in pre-clinical species. Difluoroethylamine compounds exhibit a similar potency against cathepsin K and selectivity profile against other cathepsins when compared to trifluoroethylamine analogs.

Full Text

Duke Authors

Cited Authors

  • Isabel, E; Mellon, C; Boyd, MJ; Chauret, N; Deschênes, D; Desmarais, S; Falgueyret, J-P; Gauthier, JY; Khougaz, K; Lau, CK; Léger, S; Levorse, DA; Li, CS; Massé, F; Percival, MD; Roy, B; Scheigetz, J; Thérien, M; Truong, VL; Wesolowski, G; Young, RN; Zamboni, R; Black, WC

Published Date

  • February 2011

Published In

Volume / Issue

  • 21 / 3

Start / End Page

  • 920 - 923

PubMed ID

  • 21232956

Electronic International Standard Serial Number (EISSN)

  • 1464-3405

International Standard Serial Number (ISSN)

  • 0960-894X

Digital Object Identifier (DOI)

  • 10.1016/j.bmcl.2010.12.070

Language

  • eng