6 research outputs found
Key steps in the structure-based optimization of the hepatitis C virus NS3/4A protease inhibitor SCH503034
Get PDFCrystal structures of protease/inhibitor complexes guided optimization of the buried nonpolar surface area thereby maximizing hydrophobic binding. The resulting potent tripeptide inhibitor is in clinical trials
Human Interleukin 4 Receptor Complex: Neutralization Effect of Two Monoclonal Antibodies
No full textMolecular views of viral polyprotein processing revealed by the crystal structure of the hepatitis C virus bifunctional protease–helicase
No full textDiscovery of Novel 3,3-Disubstituted Piperidines as Orally Bioavailable, Potent, and Efficacious HDM2-p53 Inhibitors
No full textA new subseries of substituted piperidines
as p53-HDM2 inhibitors
exemplified by <b>21</b> has been developed from the initial
lead <b>1</b>. Research focused on optimization of a crucial
HDM2 Trp23–ligand interaction led to the identification of
2-(trifluoromethyl)thiophene as the preferred moiety. Further investigation
of the Leu26 pocket resulted in potent, novel substituted piperidine
inhibitors of the HDM2-p53 interaction that demonstrated tumor regression
in several human cancer xenograft models in mice. The structure of
HDM2 in complex with inhibitors <b>3</b>, <b>10</b>, and <b>21</b> is described
