High-throughput synthesis of azide libraries suitable for direct "click" chemistry and in situ screening.
A key challenge in current drug discovery is the development of high-throughput (HT) amenable chemical reactions that allow rapid synthesis of diverse chemical libraries of enzyme inhibitors. The Cu(I)-catalyzed, 1,3-dipolar cycloaddition between an azide and an alkyne, better known as "click chemistry", is one such method that has received the most attention in recent years. Despite its popularity, there is still a lack of robust and efficient chemical strategies that give access to diverse libraries of azide-containing building blocks (key components in click chemistry). We report herein a highly robust and efficient strategy for high-throughput synthesis of a 325-member azide library. The method is highlighted by its simplicity and product purity. The utility of the library is demonstrated with the subsequent "click" synthesis of the corresponding bidentate inhibitors against PTP1B.
Srinivasan
Rajavel
R
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543.
Tan
Lay Pheng
LP
Wu
Hao
H
Yang
Peng-Yu
PY
Kalesh
Karunakaran A
KA
Yao
Shao Q
SQ
D001386:Azides / Q000138:chemical synthesis* / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000494:pharmacology
D001386:Azides; D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1