Details

Autor(en) / Beteiligte

• Massarotti, Alberto
• Aprile, Silvio
• Mercalli, Valentina
• Del Grosso, Erika
• Grosa, Giorgio
• Sorba, Giovanni
• Tron, Gian Cesare

Titel

Are 1,4- and 1,5-Disubstituted 1,2,3-Triazoles Good Pharmacophoric Groups?

Ist Teil von

• ChemMedChem, 2014-11, Vol.9 (11), p.2497-2508

Ort / Verlag

Weinheim: WILEY-VCH Verlag

Erscheinungsjahr

2014

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Over the last decade, 1,2,3‐triazoles have received increasing attention in medicinal chemistry thanks to the discovery of the highly useful and widely applicable 1,3‐dipolar cycloaddition reaction between azides and alkynes (click chemistry) catalyzed by copper salts and ruthenium complexes. After a decade of medicinal chemistry research on 1,2,3‐triazoles, we feel that the time is ripe to demonstrate the real ability of this heterocycle to participate in important and pivotal binding interactions with biological targets while maintaining a good pharmacokinetic profile. In this study, we retrieved and analyzed X‐ray crystal structures of complexes between 1,2,3‐triazoles and either proteins or DNA to understand the pharmacophoric role of the triazole. Furthermore, the metabolic stability, the capacity to inhibit cytochromes, and the contribution of 1,2,3‐triazoles to the overall aqueous solubility of compounds containing them have been analyzed. This information should furnish fresh insight for medicinal chemists in the design of novel bioactive molecules that contain the triazole nucleus. The time is ripe to demonstrate the real ability of 1,2,3‐triazoles to play a pivotal role in drug–receptor interactions. We analyzed the X‐ray crystal structures of 1,2,3‐triazole‐containing protein complexes to understand their pharmacophoric role. Furthermore, the metabolic stability, the ability to inhibit cytochromes, and the aqueous solubility contribution of the 1,2,3‐triazole nucleus were analyzed.