VX-950 is a potent, selective, peptidomimetic inhibitor of the hepatitis C virus (HCV) NS3-4A
serine protease, and it demonstrated excellent antiviral activity both in genotype 1b HCV …

Publisher Summary This chapter briefly reviews the use of deuterium to alter the metabolic
properties of compounds and discusses the past and current development of potential …

This research was performed to determine whether a selective inhibitor of the calcium-dependent
protease, calpain, could reduce ischemia-associated brain damage when peripherally …

Selective replacement of hydrogen atoms with deuterium (deuteration) has the unique benefit
of retaining the pharmacologic profile of physiologically active compounds while, in certain …

Infection by hepatitis C viruses (HCVs) is a serious medical problem with no broadly effective
treatment available for the progression of chronic hepatitis. The catalytic activity of a viral …

Ivacaftor is currently used for the treatment of cystic fibrosis as both monotherapy (Kalydeco;
Vertex Pharmaceuticals, Boston, MA) and combination therapy with lumacaftor (Orkambi; …

Peptidyl-keto amides have been synthesized and tested as inhibitors of the cysteine protease
calpain. A stereospecific synthesis was devised in which Cbz-dipeptidyl-a-hydroxy amides …

Selective deuterium substitution as a means of ameliorating clinically relevant pharmacokinetic
drug interactions is demonstrated in this study. Carbon-deuterium bonds are more stable …

The α-ketoamide warhead (eg, 15) was found to be a practical replacement for aliphatic
aldehydes in a series of HCV NS3· 4A protease inhibitors. Structure–activity relationships …

The use of deuterium substitution in an effort to produce kinetic isotope effects (KIEs) that
favorably alter pharmacokinetics and metabolism in drug discovery has accelerated in the last …