Chiba P, Burghofer S, Richter E, Tell B, Moser A, Ecker G
Institute of Pharmaceutical Chemistry, University of Vienna, Austria.
J Med Chem. 1995 Jul 7;38(14):2789-93. doi: 10.1021/jm00014a031.
A series of [(o-acylaryl)oxy]propanolamines have been prepared and evaluated for multidrug resistance-reverting activity in a human tumor cell model. Structure-activity relationship studies indicate that the phenylpropiophenone moiety as well as the substitution pattern at the nitrogen atom is crucial for activity of the compounds. Incorporation of the ether oxygen into a benzofuran substructure, which renders the compound an arylethanolamine, decreased biologic activity. Highest activity could be observed with the arylpiparazines 4f-h, which not only completely restored daunomycin sensitivity but also showed moderate activity in restoring etoposide toxicity.
已制备了一系列[(邻酰基芳基)氧基]丙醇胺，并在人肿瘤细胞模型中评估了它们的多药耐药逆转活性。构效关系研究表明，苯丙酰苯部分以及氮原子上的取代模式对化合物的活性至关重要。将醚氧引入苯并呋喃亚结构中，使化合物成为芳基乙醇胺，会降低生物活性。芳基哌嗪4f-h表现出最高活性，它们不仅能完全恢复柔红霉素敏感性，还在恢复依托泊苷毒性方面表现出中等活性。
