Merck Frosst Centre for Therapeutic Research, Kirkland, Québec, Canada.
Bioorg Med Chem Lett. 2011 Feb 1;21(3):920-3. doi: 10.1016/j.bmcl.2010.12.070. Epub 2010 Dec 19.
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.
在 odanacatib 等组织蛋白酶 K 抑制剂中发现的三氟乙胺基团可以被二氟乙胺基团取代。这种变化增加了氮的碱性，对 log D 产生了积极影响。这转化为临床前物种中改善的口服生物利用度。与三氟乙胺类似物相比，二氟乙胺化合物对组织蛋白酶 K 具有相似的效力和对其他组织蛋白酶的选择性。
