Synthesis, Affinity for Central Benzodiazepine Receptors, and Hypnosedative and Anxiolytic Properties of 3-Acyloxy-5-Aryl-7-Bromo-1,2-Dihydro-3H-1,4-Benzodiazepin-2-Ones

Abstract

3-Acyloxy-5-aryl-7-bromo-1,2-dihydro-3H-1,4-benzodiazepin-2-ones (3 – 18) were synthesized and shown to possess (ED₅₀ = 0.05 – 5 mg/kg) hypnotic, sedative, anticonvulsant, and anxiolytic properties. The hypnotic activity of the tested compounds varied in the dose range 0.22 – 1.50 mg/kg i.p. in mice. The pharmacological properties of 3 – 14 were comparable to those of cinazepam (Levana^® IC) and its metabolite 3-hydroxyphenazepam. The CBDR affinity was shown to increase with acyl length in the series C2-C5 whereas it decreased significantly in the series C6-C8. The tested compounds were characterized by low toxicity with LD₅₀ > 650 mg/kg i.p. in mice.