Feyns L V, Beisler J A, Driscoll J S, Adamson R A
J Pharm Sci. 1980 Feb;69(2):190-2. doi: 10.1002/jps.2600690219.
A nitrogen mustard analog of propranolol was synthesized as a potential lung-specific antitumor agent. Since dl-propranolol concentrates in lung tissue and beta-blocking activity resides only with the l-enantiomer, the d-modification could serve as a lung-directed carrier for a cytotoxic group. Reaction of 1-(1-naphthyloxy)-3-[bis(2-hydroxyethyl)amino]-2-propanol with thionyl chloride resulted in replacement of all three hydroxyl groups with chlorine. The necessary chlorination selectivity was achieved with p-toluenesulfonyl chloride in dimethylformamide solution to provide propranolol mustard, 1-(1-naphthyloxy)-3-[bis(2-chloroethyl)amino]-2-propanol. Both the trichloro compound and propranolol mustard showed reproducible activity against P-388 leukemia. Neither compound was active against the B16 tumor or Lewis lung carcinoma.
合成了一种普萘洛尔的氮芥类似物，作为一种潜在的肺特异性抗肿瘤药物。由于消旋普萘洛尔集中在肺组织中，且β-阻断活性仅存在于左旋对映体中，右旋修饰物可作为细胞毒性基团的肺导向载体。1-(1-萘氧基)-3-[双(2-羟乙基)氨基]-2-丙醇与亚硫酰氯反应，使所有三个羟基被氯取代。在二甲基甲酰胺溶液中用对甲苯磺酰氯实现了必要的氯化选择性，得到了普萘洛尔氮芥，即1-(1-萘氧基)-3-[双(2-氯乙基)氨基]-2-丙醇。三氯化合物和普萘洛尔氮芥对P-388白血病均表现出可重复的活性。这两种化合物对B16肿瘤或Lewis肺癌均无活性。
