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Bioorg Med Chem Lett. 2005 Nov 1;15(21):4741-4.

Trifluoroethylamines as amide isosteres in inhibitors of cathepsin K.

Author information

1
Merck Frosst Centre for Therapeutic Research, P.O. Box 1005, Pointe-Claire-Dorval, Que., Canada H9R 4P8. blackc@merck.com

Abstract

The P2-P3 amide of dipeptide cathepsin K inhibitors can be replaced by the metabolically stable trifluoroethylamine group. The non-basic nature of the nitrogen allows the important hydrogen bond to Gly66 to be made. The resulting compounds are 10- to 20-fold more potent than the corresponding amide derivatives. Compound 8 is a 5 pM inhibitor of human cathepsin K with >10,000-fold selectivity over other cathepsins.

PMID:
16154747
DOI:
10.1016/j.bmcl.2005.07.071
[Indexed for MEDLINE]

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