海因类化合物的合成和生物活性

海因类化合物是指含有各种取代基的五元杂环化合物,其衍生物可作为合成医药产品、杀虫剂、杀菌消毒剂及感光材料的重要中间体,开发海因类化合物具有重要意义。以3-溴苯乙酸为原料,7-溴-2-四氢萘酮为中间体,采用Ullman反应,Suzuki反应,Bucherer-Begs反应为关键步骤合成海因类化合物,关键中间体及目标分子的结构经核磁共振氢谱、碳谱得到确认。将目标化合物灌胃给药后,采用氨水引咳法以超声雾化器喷雾氨水刺激小鼠呼吸道,记录致咳潜伏期和2 min内咳嗽次数,动物试验结果表明,目标化合物能减少雾化氨水致小鼠咳嗽的次数,并延长咳嗽的潜伏期,对小鼠氨水引发的咳嗽有显著的镇咳作用,为海因类化合物的应用开发奠定基础。研究亮点:以3-溴苯乙酸为原料,7-溴-2-四氢萘酮为中间体,采用Ullman反应,Suzuki反应,Bucherer-Begs反应为关键步骤合成海因类化合物,关键中间体及目标分子的结构经核磁共振氢谱、碳谱得到确认,动物试验结果表明,目标化合物对小鼠氨水引发的咳嗽有显著的镇咳作用。

Synthesis and bioactivity of hydantoin compounds

Hydantoin compounds were a kind of five-membered heterocyclic compounds,and its derivatives could be used as important intermediate of pharmaceutical products,pesticides,disinfectant,photographic materials.The development of hydantoin compounds had great significance.In this paper,a series of new hydantoin compounds were synthesized by 3-bromo phenylacetic acid as starting material,7-bromo-2-tetralone as intermediate and with Ullmann reaction,Suzuki reaction and Bucherer-Begs reaction as key steps.The structures of key intermediate and target compounds were confirmed by 1H NMR and 13C NMR.Bioactivity of target compounds was tested by the mode of oral administration and then using ammonia water induced cough model,respiratory tract of the mice was stimulated by ammonia with ultrasound nebuliser,and record the cough incubation period of mice and the cough times within two minutes.Bioactivity research showed that the target compounds could reduce ammonia spray frequency cough in mice,extend the cough incubation period,had significant antitussive effect on mice of ammonia-induced cough,and that could lay the basis for hydantoin compounds application development.