Solid-phase synthesis of azidomethylene inhibitors targeting cysteine proteases.
An efficient strategy for the solid-phase synthesis of azidomethylene inhibitors targeting cysteine proteases is described. The method is highlighted by its compatibility with readily available building blocks, as well as its ability to accommodate different functional groups. A 249-member library has thus far been successfully synthesized, characterized, and screened against Caspase-1, -3 and -7.
Yang
Peng-Yu
PY
Department of Chemistry, NUS MedChem Program of the Office of Life Sciences, National University of Singapore, Singapore 117543.
Wu
Hao
H
Lee
Mei Yin
MY
Xu
Ashley
A
Srinivasan
Rajavel
R
Yao
Shao Q
SQ
D001386:Azides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020170:Caspase 1 / Q000737:chemistry; D053148:Caspase 3 / Q000737:chemistry; D053179:Caspase 7 / Q000737:chemistry; D061945:Caspase Inhibitors; D020650:Combinatorial Chemistry Techniques; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D008697:Methane / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D054852:Small Molecule Libraries; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001386:Azides; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D054852:Small Molecule Libraries; D053148:Caspase 3; D053179:Caspase 7; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D008697:Methane