Click Chemistry: 1,2,3‐Triazoles as Pharmacophores

Abstract

The copper(I)-catalyzed 1,2,3-triazole-forming reaction between azides and terminal alkynes has become the gold standard of click chemistry due to its reliability, specificity, and biocompatibility. Applications of click chemistry are increasingly found in all aspects of drug discovery; they range from lead finding through combinatorial chemistry and target-templated in vitro chemistry, to proteomics and DNA research by using bioconjugation reactions. The triazole products are more than just passive linkers; they readily associate with biological targets, through hydrogen-bonding and dipole interactions. The present review will focus mainly on the recent literature for applications of this reaction in the field of medicinal chemistry, in particular on use of the 1,2,3-triazole moiety as pharmacophore.

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

“…Triazoles are stable compounds with interesting properties, 1 but an important application of this reaction has also been as a method for connecting or 'clicking together' two molecules with each other, providing an alternative to amide bond formation which has traditionally filled this role.…”

Metal-catalyzed azide-alkyne “click” reactions: Mechanistic overview and recent trends

“…The concept of "click chemistry" proposed by Kolb, Finn and Sharpless in 2001 [1] has revolutionized molecular engineering including applications to organic and medicinal chemistry [2][3][4][5][6][7][8][9][10][11], polymer science and materials science [12][13][14][15][16][17][18][19][20][21]. Among the various "click" reactions responding to the requirements of this concept, the most generally used one is the copper(I)-catalyzed reaction between terminal alkynes and azides (CuAAC) selectively yielding 1,4-disubstituted 1,2,3-triazoles, that was reported independently by the Sharpless-Fokin [22] and the Meldal groups in 2002 [ 23,24].…”

1,3-Dipolarna cikloadicija (I. dio): Dobivanje 1,2,3-triazolnih derivata u nukleozidnoj kemiji

“…90 Pored brojnih primjera prisutnosti 1,2,3-triazola kao strukturnog motiva molekula s biološkom aktivnošću, 1,2,3-triazolni heterocikli pronašli su i širu industrijsku primjenu. Tako se danas upotrebljavaju kao boje i fotostabilizatori u industriji optičkih vlakana, 91 inhibitori korozije metala i legura, 92 svjetlosni stabilizatori organskih materijala i polimera te u agronomiji kao insekticidi, 93 fungicidi, 94 herbicidi i regulatori rasta.…”