Synthesis and evaluation of novel substituted 1,2,3-triazolyldihydroquinolines as promising antitubercular agents

摘要

A series of novel substituted 1,2,3-triazolyldihydroquinolines 6a-o was designed and synthesized from 2-acetylthiophene in five-step reaction sequence involving modified Boltzmann-Rahtz reaction of 13-Enaminone; Vilsmeier-Haack chloroformylation using DMF/POCl3; Ohira-Bestmann homologation of aldehyde to alkyne as key steps. The reaction of alkyne 4 with various aryl azides in the presence of copper sulfate and sodium ascorbate resulted desired new 1,2,3-triazolyldihydroquinolines 6a-o in excellent yields. In vitro screening of new compounds for anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv (Mtb), resulted in three derivatives 6a (MIC:1.56 mu g/mL) and 6d, 61 (MIC:3.12 mu g/mL) as promising antitubercular agents with lower cytotoxicity profiles.