A click chemistry approach for the synthesis of mono and bis aryloxy linked coumarinyl triazoles as anti-tubercular agents

作者：Anand Ashish; Naik Reshma J; Revankar Hrishikesh M; Kulkarni Manohar V^*; Dixit Sheshagiri R; Joshi Shrinivas D

来源：European Journal of Medicinal Chemistry, 2015, 105: 194-207.

DOI：10.1016/j.ejmech.2015.10.019

• 1,2,3 triazoles
• Click reaction
• 2H-chromen-2-one
• Anti-tubercular
• Molecular docking
• Surflex-dock
• 3D-QSAR

A series of mono and bis-triazole coumarin hybrids 6a-u and 9a-f respectively have been synthesized using 4-(azidomethyl)-2H-chromen-2-ones 5a-i and aryl propargyl ethers 2a-c/8 employing Click chemistry modified protocol for Azide-Alkyne cycloadditions(CuAAC). Anti-tubercular screening showed moderate activity for mono aryloxy compounds 6a-u with MIC 50-100 mu g/mL, whereas the bis compounds 9a-f were more effective with MICs between 0.2 and 12.5 mu g/mL. Molecular modeling and 3D-QSAR measurements using CoMFA and Topomer CoMFA further supported the observed results. The his compound 9b showed excellent activity with MIC value as low as 0.2 mu g/mL.

• 出版日期2015-11-13