Trifluoromethylphenyl as P2 for ketoamide-based cathepsin S inhibitors
Jiaqiang Cai1, John Robinson, Simone Belshaw
1Merck Research Laboratories, MSD, Newhouse, Lanarkshire, United Kingdom. jiaqiang.cai@merck.com
Bioorganic & Medicinal Chemistry Letters
|October 30, 2010
Abstract:
The trifluoromethylphenyl P2 motif from previously reported heteroarylnitrile series has been successfully applied for the design and synthesis of highly potent novel ketoamide-based cathepsin S inhibitors. The key in this process is the change of the torsion angle between the P2 phenyl ring and the attached secondary amide by adding a small Cl, F, or Me group at the 2-position.

