Zhang S, Powell M L, Nelson W L, Wirth P J
J Med Chem. 1983 Mar;26(3):455-8. doi: 10.1021/jm00357a027.
Potential precursors to chemically reactive species derived from the beta-adrenergic antagonist propranolol were synthesized and tested for mutagenicity in the Ames Salmonella assay. N-Hydroxypropranolol (1), the corresponding aldonitrone, 3-(1-naphthoxy)-2-hydroxypropionaldehyde N-isopropylnitrone (2), and N-nitrosopropranolol (3) were prepared and tested. N-Hydroxypropranolol (1) was obtained by direct alkylation of 3-(1-naphthoxy)-1-bromo-2-propanol with N-isopropylhydroxylamine and isolated as its neutral oxalate or HBr salt. The aldonitrone (2) was obtained by mercuric oxide oxidation of the hydroxylamine. N-Nitrosopropranolol (3) was prepared by treating propranolol with nitrous acid. None of the compounds was mutagenic in the Ames assay with Salmonella typhimurium TA-98 and TA-100 strains, either in the absence or in the presence of the S-9 liver fraction from Arochlor 1254 treated rats. None of the compounds was significantly toxic to the bacteria, except for slight toxicity of the oxalate salt of 1.
合成了源自β-肾上腺素能拮抗剂普萘洛尔的化学反应性物种的潜在前体，并在艾姆斯沙门氏菌试验中测试其致突变性。制备并测试了N-羟基普萘洛尔（1）、相应的醛肟（3-(1-萘氧基)-2-羟基丙醛N-异丙基亚硝酮，2）和N-亚硝基普萘洛尔（3）。N-羟基普萘洛尔（1）通过3-(1-萘氧基)-1-溴-2-丙醇与N-异丙基羟胺直接烷基化反应制得，并以其中性草酸盐或氢溴酸盐形式分离出来。醛肟（2）通过用氧化汞氧化羟胺制得。N-亚硝基普萘洛尔（3）通过用亚硝酸处理普萘洛尔制备。在鼠伤寒沙门氏菌TA-98和TA-100菌株的艾姆斯试验中，无论在不存在或存在来自经多氯联苯混合物1254处理大鼠的S-9肝匀浆的情况下，这些化合物均无致突变性。除了1的草酸盐有轻微毒性外，这些化合物对细菌均无明显毒性。
