Synthesis Of New Sedative-Hypnotic Drug Zaleplon And Its Analogues

Zaleplon,as a new pyrazolopyrimidines sedative-hypnotic drug, was developed by Wyeth-Ayerst company of the United States. It is a full agonist of BZ1(1) receptor and produces inhibition of CNS by acting at GABAa receptors complexes. In this paper, sleep psysiology, development of sedative and hypnotics, the pharmacology, pharmacokinetics, pharmacodynamics and clinical appropriations of zaleplon are reviewed.The target compound was synthesized from acetophenone by the reaction of nitration, reduction, acylation, condensation, alkylation and cyclization, and the structure of zaleplon was confirmed by 1HNMRJR and MS. In the condensation reaction,the method of the product's purification in the literature was tedious,and by many trials,we found that the product was pure enough by recrystallizing from toluene.The method is simpler than that in the literature.In the hydrocarbylation reaction,bromoethane was used instead of the expensive iodoethane with the yield 90% and the cost was reduced.Besides sedative-hypnotic activity,compounds of pyrazolopyrimidines have the activity of phosphodiesterase inhibitory effect. In order to find some compounds with pharmacological activities,we changed the substitutes of pyrazolo[l,5-a]pyrimidine with zaleplon as a lead compound.Nineteen pyrazolo[l,5-a]pyrimidines compounds, including six 3,7-disubstituded,one 3,6,7-trisubstituded and twelve 3,5,7- trisubstituded compounds,were designed and synthesized, and their structures were identified by 1HNMR and IR.The pharmacological test is on the way...