...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Medicinal Chemistry >Preclinical Activity of New [1,2]Oxazolo[5,4-e]isoindole Derivatives in Diffuse Malignant Peritoneal Mesothelioma
【24h】

Preclinical Activity of New [1,2]Oxazolo[5,4-e]isoindole Derivatives in Diffuse Malignant Peritoneal Mesothelioma

机译：新的[1,2] O唑[5,4-e]异吲哚衍生物在弥漫性恶性腹膜间皮瘤中的临床前活性

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

A series of 22 derivatives of the [1,2]oxazolo[5,4-e]isoindole system were synthesized through an efficient and versatile procedure that involves the annelation of the [1,2] oxazole moiety to the isoindole ring, producing derivatives with a wide substitution pattern. The structure activity relationship indicates that the N-4-methoxybenzyl group appears crucial for potent activity. In addition, the presence of a 6-phenyl moiety is important and the best activity is reached with a 3,4,5-trimethoxy substituent. The most active compound, bearing both the structural features, was able to inhibit tumor cell proliferation at nanomolar concentrations when tested against the full NCI human tumor cell line panel. Interestingly, this compound was effective in reducing in vitro and in vivo cell growth, impairing cell cycle progression and inducing apoptosis, as a consequence of the inhibition of tubulin polymerization, in experimental models of diffuse malignant peritoneal mesothelioma (DMPM), a rapidly lethal disease, poorly responsive to conventional therapeutic strategies.
机译：[1,2]恶唑并[5,4-e]异吲哚系统的一系列22种衍生物是通过有效且通用的方法合成的，该方法涉及将[1,2]恶唑部分环化到异吲哚环上，从而产生衍生物具有广泛的替代模式。结构活性关系表明N-4-甲氧基苄基似乎对有效活性至关重要。另外，6-苯基部分的存在是重要的，并且用3,4,5-三甲氧基取代基达到最佳活性。当对整个NCI人肿瘤细胞系进行测试时，具有两种结构特征的最具活性的化合物能够在纳摩尔浓度下抑制肿瘤细胞的增殖。有趣的是，由于微管蛋白聚合的抑制作用，在弥漫性恶性腹膜间皮瘤（DMPM）（一种快速致死性疾病）的实验模型中，该化合物可有效降低体外和体内细胞生长，削弱细胞周期进程并诱导凋亡。 ，对常规治疗策略的反应较差。

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