苯乙醇胺类化合物的合成及其抗哮喘活性研究

Synthesis and anti-asthma activities of phenylethanolamine derivatives

目的设计合成2-胺基-1-苯基乙醇类化合物并研究其抗哮喘活性。方法以取代苯乙酮为原料,经α-溴代、胺解、还原、成盐等反应合成目标化合物,采用离体豚鼠气管条法和β2-肾上腺素受体激动剂钙流筛选模型测定目标化合物的药理活性。结果设计并合成了15个苯乙醇胺类化合物,其中12个化合物是未见文献报道的新化合物,其结构均经过1H-NMR及MS谱确证。结论所合成的化合物初步证明为2β-肾上腺素受体激动剂,具有不同程度的支气管舒张作用,其中化合物1a^1d显示出较好的活性,值得进一步深入研究。

Aim To design and synthesize 2-amino-l-phenylethanol derivatives and to evaluate their anti-asthma activities. Methods The target compounds were synthesized from substituted acetophenones via a-bromination, amination, reduction and salt-formation. And their effects on guinea-pig tracheal smooth muscle and β2-adrenoceptor were determined. Results Fifteen compounds were synthesized and twelve compounds were first reported. All the structures were confirmed by ^1H-NMR and MS. Conclusion Preliminary pharmacological studies revealed that the novel derivatives were β2-adrenoceptor agonists possessing relaxing activities on the contracting bronchial smooth muscle of guinea-pigs induced by histamine. Among them,la-ld exhibited high activities and were worthy of further investigation.