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5-Lipoxygenase (5-LO) is the key enzyme responsible for the conversion of arachidonic acid to leukotrienes, a class of lipid mediators implicated in inflammatory disorders. In this paper, we describe the design, synthesis, and preliminary activity studies of novel clicked caffeic esters and amides as radical scavengers and 5-LO inhibitors. From known 5-LO inhibitor 3 as a lead, cinnamic esters 8a–h and amides 9a–h as well as caffeic esters 15a–h and amides 16a–h were synthesized by Cu(I)-catalyzed [1,3]-dipolar cycloaddition with the appropriate azide precursors and terminal alkynes. All caffeic analogs are proved to be good radical scavengers (IC50: 10–20 μM). Esters 15g and 15f possessed excellent 5-LO inhibition activity in HEK293 cells and were equipotent with the known 5-LO inhibitor CAPE and more potent than Zileuton. Several synthesized esters possess activities rivaling Zileuton in stimulated human polymorphonuclear leukocytes.

Synthesis and Structure-Activity Relationship of 1-and 2-Substituted 1,2,3-Triazole Letrozole-Based Analogues as Aromatase Inhibitors. -1,2,3-Triazole analogues, e.g. (III) and (V), of letrozole are synthesized by employing the "click" chemistry as the key step. The presence of a para-cyano group and two aryl groups seems to be important for good activity. Compounds (IIIe) and (Ve) could serve as potential lead compounds. -(DOIRON, J.; SOULTAN, A. H.; RICHARD, R.; TOURE, M. M.; PICOT, N.; RICHARD, R.; CUPERLOVIC-CULF, M.; ROBICHAUD, G. A.; TOUAIBIA*, M.; Eur. J. Med. Chem. 46 (2011) 9, 4010-4024, http://dx.