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Difluoroethylamines as an amide isostere in inhibitors of cathepsin K.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2011 Feb 01; Vol. 21 (3), pp. 920-3. Date of Electronic Publication: 2010 Dec 19. - Publication Year :
- 2011
-
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.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Subjects :
- Administration, Oral
Amides chemistry
Animals
Biphenyl Compounds chemistry
Biphenyl Compounds pharmacology
Cathepsin K metabolism
Dogs
Ethylamines chemical synthesis
Ethylamines pharmacokinetics
Protease Inhibitors chemical synthesis
Protease Inhibitors pharmacokinetics
Rats
Cathepsin K antagonists & inhibitors
Ethylamines chemistry
Protease Inhibitors chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 21
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 21232956
- Full Text :
- https://doi.org/10.1016/j.bmcl.2010.12.070