Click chemistry reactions in medicinal chemistry: Applications of the 1,3‐dipolar cycloaddition between azides and alkynes

Abstract

In recent years, there has been an ever-increasing need for rapid reactions that meet the three main criteria of an ideal synthesis: efficiency, versatility, and selectivity. Such reactions would allow medicinal chemistry to keep pace with the multitude of information derived from modern biological screening techniques. The present review describes one of these reactions, the 1,3-dipolar cycloaddition ("click-reaction") between azides and alkynes catalyzed by copper (I) salts. The simplicity of this reaction and the ease of purification of the resulting products have opened new opportunities in generating vast arrays of compounds with biological potential. The present review will outline the accomplishments of this strategy achieved so far and outline some of medicinal chemistry applications in which click-chemistry might be relevant in the future.

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].…”

1,2,4‐Trisubstituted Cyclopentanes as Platforms for Diversity

“…For example, the amino group can be selectively acylated in the presence of the hydroxy and azido groups; the hydroxy group can be selectively silylated, and organic azides undergo 3 þ 2 cycloaddition reactions with alkynes. The latter reaction has become firmly established as a tool for medicinal chemists [21][22][23][24].…”

Regioselective Click Chemistry for Construction of Arylpiperazinyl 1,2,3-Triazole Derivative Libraries as Dopamine D4/D3Receptor Ligands

“…3 In particular, 1,2,3-triazole structures have been the key bioisostere for medicinal chemistry due to their wide applicability in the drug development fields. 4,5 However, with the exception of our previous report, 6 no report has been issued on application of click chemistry for disubstituted 1,2,3-triazole derivatives as dopamine receptors ligands.…”