Synthesis of 1,4-disubstituted 1,2,3-triazole Derivatives Using Click Chemistry and their Src Kinase Activities

Alexandre Lebeau (1) , Cyril Abrioux (2) , David Bénimèlis (3) , Zohra Benfodda (3) , Patrick Meffre (3)

1 AGROCAMPUS OUEST
2 ICGM - Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier
3 CHROME - Détection, évaluation, gestion des risques CHROniques et éMErgents (CHROME) / Université de Nîmes

A series of 1,4-disubstituted 1,2,3-triazoles derivatives (3) were designed and prepared as potential inhibitors for Src kinase. In this manuscript, all of the designed compounds were screened via molecular docking using PLANTS as virtual screening software to identify new inhibitors of Src kinase. As expected, the results of the docking study revealed that most of these targeted compounds possessed low binding energy. Subsequently, all of the screened compounds were synthesized via Huisgen's 1,3-dipolar cycloaddition between terminal alkynes (1) and methyl 2-azidoacetate (2) with Cu(I) in excellent yields at room temperature. The synthesized triazoles (3) were characterized by IR, 1 H, 13 C, 19 F NMR and mass spectral techniques and they were investigated as inhibitors of Src kinase. Among these compounds, 3m exhibited the most potent inhibitory activity against Src kinase.

Mots clés: Click chemistry; Src kinase; 1 2 3-triazole; molecular docking; Huisgen's 1 3-dipolar cycloaddition; PEG400

Domaines: Génie chimique; Chimie organique

Alexandre Lebeau, Cyril Abrioux, David Bénimèlis, Zohra Benfodda, Patrick Meffre. Synthesis of 1,4-disubstituted 1,2,3-triazole Derivatives Using Click Chemistry and their Src Kinase Activities. Medicinal Chemistry, 2017, Medicinal Chemistry, 13, pp.40-48. ⟨10.2174/1573406412666160404125718⟩. ⟨hal-01495029⟩