Some reactions of 1,4-dihydropyridines with organic azides. Synthesis of 2,7-diazabicyclo[4.1.0]hept-3-enes with analgesic and antiprotozoal activity

Abstract

The 1,3-dipolar cycloaddition reaction of 1,4-dihydropyridines with organic azides afford 2,7-diazabicyclo[4.1.0]hept-3-enes, 4, which exhibit significant analgesic and antiprotozoal activities. The most active analgesics in mice, 4a [2-methyl-7-cyano-2,7-diazobicyclo[4.1.0]hept-3-ene] and 4c [2-methyl-7-(benzenesulfonyl)-2,7-diazabicyclo[4.1.0]-hept-3-ene], were more potent than aspirin or dextropropoxyphene. Diazabicyclo[4.1.0]hept-3-enes exert potent antiprotozoal activity, inhibiting growth of Trichomonas vaginalis at concentrations of < 10 .mu.g/ml of medium. The broad spectrum pharmacological screen revealed moderate hypoglycemic (4a), antiinflammatory (4c), antidepressant [2-methyl-7-[(p-acetamidobenzene)sulfonyl]-2,7-diazabicyclo[4.1.0]hept-3-ene] and [2-methyl-7-[(p-aminobenzene)sulfonyl]-2,7-diazabicyclo[4.1.0]hept-3-ene] in rats and antihistaminic [7-(benzenesulfonyl)-2,7-diazabicyclo[4.1.0]hept-3-ene] activities in guinea pigs.