POTENTIAL ANTILEUKEMIC AND IMMUNOSUPPRESSIVE DRUGS .3. EFFECTS OF HOMOCYCLIC RING SUBSTITUTION ON IN-VITRO DRUG ACTIVITY OF 4-NITROBENZO-2,1,3-OXADIAZOLES (4-NITROBENZOFURAZANS) AND THEIR N-OXIDES (4-NITROBENZOFUROXANS)
POTENTIAL ANTILEUKEMIC AND IMMUNOSUPPRESSIVE DRUGS .3. EFFECTS OF HOMOCYCLIC RING SUBSTITUTION ON IN-VITRO DRUG ACTIVITY OF 4-NITROBENZO-2,1,3-OXADIAZOLES (4-NITROBENZOFURAZANS) AND THEIR N-OXIDES (4-NITROBENZOFUROXANS)
复制标题
DOI：
10.1021/jm00273a012
复制
发表时间：
1972-01-01
影响因子：
7.3
通讯作者：
TERNAI, B
中科院分区：
文献类型：
--
作者：
GHOSH, PB;WHITEHOUSE, MW;TERNAI, B
4-已经检查了在5和6位（相对于NO2）带有吸电子取代基的硝基苯并呋咱和苯并呋咱在体外抑制兔胸腺细胞中核酸合成的能力。在该筛选中，没有测试的化合物比未取代的硝基苯并呋咱或硝基苯并氧化呋咱更有效，这表明具有细胞硫醇和氨基的Meisenheimer络合物的形成和稳定性因5位和6位的取代基的存在而减少。5-卤代（F，Cl，Br）苯并氧化呋咱在4位硝化，与将NO2引导至7位的5-CF 8，5-CN，5-CONHR和5-COOR苯并氧化呋咱相反。本文讨论了5-F（相对于5-C1或5-Br）苯并氧化呋咱的一些独特的化学和生物学性质，并指出带有NO_2基团的苯并氧化呋咱和苯并呋咱的一种可能的作用方式是在细胞水平上形成淋巴细胞核酸合成的Meisenheimer抑制剂。2.与细胞必需的巯基和/或氨基形成复合物。
4-Nitrobenzofuroxans and benzofurazans bearing electron-withdrawing substituents in the 5 and 6 positions (relative to N02) have been examined for their ability to inhibit nucleic acid synthesis in rabbit thymocytes in vitro. None of the compds tested were more potent in this screen than the unsubstituted nitrobenzofurazan or nitrobenzofuroxan, suggesting that the formation and stability of Meisenheimer complexes with cellular thiols and amino groups is diminished by the presence of substituents in the 5 as well as 6 position. The 5-halogeno (F, Cl, Br) benzofuroxans nitrated in the 4 position, in contrast to 5-CFg, 5-CN, 5-CONHR, and 5-COOR benzofuroxans which direct N02 to the 7 position. Some unique chemical and biological properties of 5-F (vs. 5-C1 or 5-Br) benzofuroxan are discussed.Benzofuroxans and benzofurazans bearing N02 groups in suggested2 that a possible mode of action of these com-the 4 and 5 positions have been shownto be potent in vitro pounds at the cellular level was by forming Meisenheimer inhibitors of nucleic acid synthesis in lymphocytes. 2 It was complexes with essential cellular SH and/or amino groups.