• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Medicinal Chemistry >Synthesis and antiviral activity of 4-benzyl pyridinone derivatives as potent and selective non-nucleoside human immunodeficiency virus type 1 reverse transcriptase inhibitors
【24h】

Synthesis and antiviral activity of 4-benzyl pyridinone derivatives as potent and selective non-nucleoside human immunodeficiency virus type 1 reverse transcriptase inhibitors

机译：4-苄基吡啶酮衍生物作为强效和选择性非核苷人类免疫缺陷病毒1型逆转录酶抑制剂的合成和抗病毒活性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Several 4-benzyl analogues of 5-ethyl-6-methyl-4-(phenylthio)pyridin-2(1H)-ones were synthesized and evaluated for their anti-HIV-l activities. Key transformations include metalation at the 4-C-position of 5-ethyl-2-methoxy-6-methyl-3-pivaloylaminopyridine (5) and its coupling with benzyl bromide or benzaldehyde derivatives. Biological studies revealed that some of the new 4-benzylpyridinones show potent HIV-1 specific reverse transcriptase inhibitory properties. Compounds 14, 19, and 27, which inhibit the replication of HIV-1 in CEM-SS cells, with IC50 values ranging from 0.2 to 6 nM are the most active compounds in this series. Biochemical studies showed that compound 27 strongly inhibited the activity of a recombinant HIV-1 RT. Moreover, the infectivity of isolated HIV-1 particles was severely decreased after exposure to compound 27. Although cross resistance is frequently observed between non-nucleoside reverse transcriptase inhibitors, compound 27 was capable of inhibiting a virus resistant to nevirapine with an IC50 Of 40 nM. [References: 41]
机译：合成了5-乙基-6-甲基-4-（苯硫基）吡啶-2（1H）-one的几种4-苄基类似物，并评估了它们的抗HIV-1活性。关键的转化包括在5-乙基-2-甲氧基-6-甲基-3-新戊酰氨基吡啶的5 -C位的金属化（5）及其与苄基溴或苯甲醛衍生物的偶联。生物学研究表明，一些新的4-苄基吡啶酮显示出有效的HIV-1特异性逆转录酶抑制特性。化合物14、19和27抑制HIV-1在CEM-SS细胞中的复制，IC50值为0.2至6 nM，是该系列中活性最高的化合物。生化研究表明，化合物27强烈抑制重组HIV-1 RT的活性。此外，暴露于化合物27后，分离出的HIV-1颗粒的感染力大大降低。尽管在非核苷类逆转录酶抑制剂之间经常观察到交叉耐药性，但化合物27能够以40 nM的IC50抑制耐奈韦拉平的病毒。 [参考：41]

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号