Difluoroethylamines as an amide isostere in inhibitors of cathepsin K

doi:10.1016/j.bmcl.2010.12.070

Bioorganic & Medicinal Chemistry Letters

Volume 21, Issue 3, 1 February 2011, Pages 920-923

https://doi.org/10.1016/j.bmcl.2010.12.070 Get rights and content

Abstract

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.

Graphical abstract

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Difluoroethylamines as an amide isostere in inhibitors of cathepsin K

Abstract

Graphical abstract

Mater. Sci. Eng., C

Bioorg. Med. Chem. Lett.

Synlett

Nat. Rev. Drug Disc.

Curr. Top. Med. Chem.

Bioorg. Med. Chem. Lett.

J. Org. Chem.

Angew. Chem., Int. Ed.