Difluoroethylamines as an amide isostere in inhibitors of cathepsin K.


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.

DOI: 10.1016/j.bmcl.2010.12.070

Cite this paper

@article{Isabel2011DifluoroethylaminesAA, title={Difluoroethylamines as an amide isostere in inhibitors of cathepsin K.}, author={Elise Isabel and Christophe Mellon and Michael J Boyd and Nathalie Chauret and Denis Desch{\^e}nes and Sylvie Desmarais and J. P. Falgueyret and Jacques Yves Gauthier and Karine Khougaz and Cheuk K Lau and Serge L{\'e}ger and Dorothy A Levorse and Chun Sing Li and Fr{\'e}d{\'e}ric Mass{\'e} and Maida Percival and Bruno Roy and John Scheigetz and Michel Th{\'e}rien and Vouy Linh Truong and Gregg A Wesolowski and Robert N Young and Robert J. Zamboni and W. Cameron Black}, journal={Bioorganic & medicinal chemistry letters}, year={2011}, volume={21 3}, pages={920-3} }