论文部分内容阅读
为了寻找一个理想的支气管扩张药,导致合成与试验了一大批基于异丙肾上腺素结构的化合物,以延长支气管扩张作用和增强β_2-选择性,从而减少因兴奋β_1-而引起的副作用发生率。最近,制备了侧链与特布他林或者舒喘宁相似的一系列化合物。这些化合物证明对β-肾上腺素能受体有较高的亲和力,溴噁特罗为其中之一,被选出作进一步评价。合成 3-溴-5-异噁唑酰氯(Ⅰ)与丙二酸二乙酯(Ⅱ)缩合得相应的丙二酰衍生物(Ⅲ),Ⅲ经脱羧水解后生成5-乙酰基-3-溴异噁唑(Ⅳ)。Ⅳ经溴化得5-溴乙酰基-3-溴异噁唑
In search of an ideal bronchodilator, a large number of isoproterenol-based compounds were synthesized and tested to prolong bronchodilation and enhance β_2-selectivity, thereby reducing the incidence of side effects caused by excited β_1. Recently, a series of compounds with side chains similar to terbutaline or salbutamol were prepared. These compounds demonstrate a higher affinity for the [beta] -adrenergic receptor, one of which is selected for further evaluation. Synthesis of 3-bromo-5-isoxazolyl chloride (I) and diethyl malonate (II) to give the corresponding malonyl derivatives (III), which are hydrolyzed by decarboxylation to give 5-acetyl- Bromoisoxazole (IV). Bromination of IV bromo-acetyl-3-bromoisoxazole