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 c...

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Veröffentlicht in:Organic & biomolecular chemistry 2009-01, Vol.7 (9), p.1821-1828
Hauptverfasser: Srinivasan, Rajavel, Tan, Lay Pheng, Wu, Hao, Yang, Peng-Yu, Kalesh, Karunakaran A, Yao, Shao Q
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container_end_page 1828
container_issue 9
container_start_page 1821
container_title Organic & biomolecular chemistry
container_volume 7
creator Srinivasan, Rajavel
Tan, Lay Pheng
Wu, Hao
Yang, Peng-Yu
Kalesh, Karunakaran A
Yao, Shao Q
description 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.
doi_str_mv 10.1039/b902338k
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subjects Azides - chemical synthesis
Azides - pharmacology
Combinatorial Chemistry Techniques
Drug Evaluation, Preclinical
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - pharmacology
Molecular Structure
Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors
Small Molecule Libraries - chemical synthesis
Small Molecule Libraries - pharmacology
title High-throughput synthesis of azide libraries suitable for direct "click" chemistry and in situ screening
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