Synthesis of Imidazole Derivatives with Antimycobacterial Activity

✍ Scribed by Pedro O. Miranda; Lise-Lotte Gundersen

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 661 KB
• Volume: 343
• Category: Article
• ISSN: 0365-6233
• DOI: 10.1002/ardp.200900149

✦ Synopsis

Abstract

4‐Substituted 1‐(p‐methoxybenzyl)imidazoles were designed and synthesized in order to mimic parts of the structure of highly potent antimycobacterial 6‐aryl‐9‐(p‐methoxybenzyl)purines. 4‐Haloimidazoles were subjected to Pd‐catalyzed cross‐coupling in order to introduce a (hetero)aryl group, or they were converted to Grignard reagents and reacted with (hetero)arylaldehydes. Further transformations of the adducts gave a variety of potential antimycobacterials with different “spacers” between the imidazole and (hetero)aryl group. The adduct from furfural was rearranged to a cyclopentenone derivative when treated with methanol under acidic conditions. Several target compounds exhibited antimycobacterial activity in vitro (IC~90~ 13 μg/mL for the best inhibitors), but they were not as active as the most potent purines and pyrimidines synthesized before.