(1R)-N-benzyl-1-[[(2R,3R,11bS)-3-ethyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizin-2-yl]methyl]-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxamide | 1393924-21-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吐根碱生物碱
• 英文名称: (1R)-N-benzyl-1-[[(2R,3R,11bS)-3-ethyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizin-2-yl]methyl]-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxamide
• CAS: 1393924-21-4
• 化学式: C₃₇H₄₇N₃O₅
• 分子量: 613.797
• InChiKey: SJMUVNLIJZJGKJ-MHXSQSGFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  45
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  72.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  苄胺 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 生成 (1R)-N-benzyl-1-[[(2R,3R,11bS)-3-ethyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizin-2-yl]methyl]-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxamide
  参考文献：
  名称：

  [EN] EMETINE DERIVATIVES, PRODRUGS CONTAINING SAME, AND METHODS OF TREATING CONDITIONS USING SAME
  [FR] DÉRIVÉS D'ÉMÉTINE, PRODROGUES CONTENANT CES DÉRIVÉS ET PROCÉDÉS DE TRAITEMENT DE TROUBLES AU MOYEN DE CES PRODROGUES

  摘要：

  本文提供了一些化合物，它们是伊美啶衍生物，可以用作前药，在特定细胞条件下选择性地发生活化以释放伊美啶。在一个方面，通过将阻断基固定到伊美啶分子上，通过在癌症/肿瘤微环境中选择性水解的方式，可以将其衍生化到N2'-位置。这种化合物比伊美啶更少细胞毒性，并在非癌细胞中基本无活性。在一个方面，本文描述的化合物可用于治疗转移性和非转移性癌症，包括乳腺癌、前列腺癌、肺癌和白血病等。

  公开号：

  WO2012162175A1

文献信息

• [EN] EMETINE DERIVATIVES, PRODRUGS CONTAINING SAME, AND METHODS OF TREATING CONDITIONS USING SAME<br/>[FR] DÉRIVÉS D'ÉMÉTINE, PRODROGUES CONTENANT CES DÉRIVÉS ET PROCÉDÉS DE TRAITEMENT DE TROUBLES AU MOYEN DE CES PRODROGUES
  申请人：UNIV HOWARD

  公开号：WO2012162175A1

  公开（公告）日：2012-11-29

  Compounds are provided herein which are emetine derivatives that can be used as prodrugs which selectively undergo activation to release emetine in specific cellular conditions. In one aspect, a blocking group is incorporated onto the emetine molecule by the derivization of the N2'-position with moieties that can be selectively removed by hydrolysis in the cancer/tumor microenvironment. Such compounds are less cytotoxic than emetine and are substantially inactive in non-cancerous cells. In one aspect, the compounds described herein can be used for the treatment of metastatic and non-metastatic cancers, including, for example, breast cancer, prostate cancer, lung cancer, and leukemia.

  本文提供了一些化合物，它们是伊美啶衍生物，可以用作前药，在特定细胞条件下选择性地发生活化以释放伊美啶。在一个方面，通过将阻断基固定到伊美啶分子上，通过在癌症/肿瘤微环境中选择性水解的方式，可以将其衍生化到N2'-位置。这种化合物比伊美啶更少细胞毒性，并在非癌细胞中基本无活性。在一个方面，本文描述的化合物可用于治疗转移性和非转移性癌症，包括乳腺癌、前列腺癌、肺癌和白血病等。
• Design, Synthesis, and Evaluation of pH-Dependent Hydrolyzable Emetine Analogues as Treatment for Prostate Cancer
  作者：Emmanuel S. Akinboye、Marc D. Rosen、Samuel R. Denmeade、Bernard Kwabi-Addo、Oladapo Bakare

  DOI：10.1021/jm300426q

  日期：2012.9.13

  The N-2' position of the natural product emetine has been derivatized to thiourea, urea, sulfonamide, dithiocarbamate, carbamate, and pH responsive hydrolyzable amide analogues. In vitro studies of these analogues in PC3 and LNCaP prostate cancer cell lines showed that the analogues are generally less cytotoxic (average IC50 ranging from 0.079 to 10 mu M) than emetine (IC50 ranging from 0.0237 to 0.0329 mu M). The pH sensitive sodium dithiocarbamate salt 13 and the amide analogues 21, 22, 26 (obtained from maleic and citraconic anhydrides) showed the most promise as acid-activatable prodrugs under mildly acidic conditions found in the cancer microenvironment. These prodrugs released 12-83% of emetine at pH 6.5 and 41-95% emetine at pH 5.5. Compounds 13 and 26 were further shown to exhibit increased cytotoxicity in PC3 cell culture medium that was already below pH 7.0 at the time of treatment.