Investigation of ketone warheads as alternatives to the nitrile for preparation of potent and selective cathepsin K inhibitors

Amino ketone warheads were explored as alternatives to the nitrile group of a potent and selective cathepsin K inhibitor. The resulting compounds were potent and selective inhibitors of cathepsin K and these nitrile replacements had a significant effect on metabolism and pharmacokinetics. (c) 2008 Elsevier Ltd. All rights reserved.