Synthesis of imidazole derivatives with antimycobacterial activity.
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 microg/mL for the best inhibitors), but they were not as active as the most potent purines and pyrimidines synthesized before.
Miranda
Pedro O
PO
Department of Chemistry, University of Oslo, Blindern, Oslo, Norway.
Gundersen
Lise-Lotte
LL
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D007093:Imidazoles