(13aS,14S)-14-hydroxy-6,7-dimethoxy-9,11,12,13,13a,14-hexahydrodibenzo[f,h]pyrrolo[1,2-b]isoquinolin-3-yl furan-2-carboxylate | 1223487-70-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: (13aS,14S)-14-hydroxy-6,7-dimethoxy-9,11,12,13,13a,14-hexahydrodibenzo[f,h]pyrrolo[1,2-b]isoquinolin-3-yl furan-2-carboxylate
• 英文别名: furan-2-carboxylic acid (12aS,13S)-13-hydroxy-6,7-dimethoxy-9,10,11,12,12a,13-hexahydro-9a-aza-cyclopenta[b]triphenylene-3-yl ester；[(13aS,14S)-14-hydroxy-6,7-dimethoxy-9,11,12,13,13a,14-hexahydrophenanthro[9,10-f]indolizin-3-yl] furan-2-carboxylate
• CAS: 1223487-70-4
• 化学式: C₂₇H₂₅NO₆
• 分子量: 459.499
• InChiKey: XBSVQGIEUHTROY-HFZDXXHNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  81.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  呋喃甲酰氯 、 13a(S),14(S)-(+)-3,14-dihydroxy-6,7-dimethoxyphenanthroindolizidine 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以66.5%的产率得到(13aS,14S)-14-hydroxy-6,7-dimethoxy-9,11,12,13,13a,14-hexahydrodibenzo[f,h]pyrrolo[1,2-b]isoquinolin-3-yl furan-2-carboxylate
  参考文献：
  名称：

  Synthesis of Phenanthroindolizidine Alkaloids with an Acyloxy Group at the C3 Position and their Antitumor Activities and Toxicities

  摘要：

  我们之前报告过，苯并吲哚烯醇真碱3及其衍生物在体外具有显著的细胞毒性。然而，它们在体内的抗肿瘤活性较低且毒性较高，这对进一步开发构成了严重问题。基于通过乙酰化3可以改善抗肿瘤活性和毒性的发现，我们合成了3的新衍生物，这些衍生物具有不同的酰基，并评估了它们的抗肿瘤活性和毒性。我们发现，具有立体较小酰基的衍生物的抗肿瘤活性得到了改善。

  DOI：

  10.2174/157018012800389232

文献信息

• PHENANTHROINDOLIZIDINE DERIVATIVE AND NFKB INHIBITOR CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：Ikeda Takashi

  公开号：US20110201637A1

  公开（公告）日：2011-08-18

  A novel compound having an excellent NFκB inhibitory effect is provided. Specifically disclosed is a compound represented by the following formula (1) or a salt thereof: wherein, R 1 represents a hydrogen atom, a lower alkyl group, or the like; R 2 represents a hydrogen atom, a lower alkyl group, a halogen atom, or the like; R 3 represents a hydrogen atom, a lower alkyl group, a hydroxyl group, or a halogen atom; R 4 represents a hydrogen atom or a lower alkyloxy group; R 5 represents a hydrogen atom, a lower alkyloxy group, a halogen atom, a hydroxyl group, or a methylenedioxy group formed together with R 6 or an isopropylidenedioxy group formed together with R 6 ; R 6 represents a hydrogen atom, a lower alkyloxy group, or a methylenedioxy group formed together with R 5 or an isopropylidenedioxy group formed together with R 5 ; R 7 represents a hydrogen atom or a lower alkyl group; and R 8 represents a hydrogen atom, a hydroxyl group, an amino group, a lower alkylcarbonyloxy group, or a halogen atom.

  提供一种具有优异的NFκB抑制效果的新化合物。具体披露的是以下式（1）或其盐的化合物：其中，R1代表氢原子，低碳基或类似物; R2代表氢原子，低碳基，卤素原子或类似物; R3代表氢原子，低碳基，羟基或卤素原子; R4代表氢原子或低碳基氧基; R5代表氢原子，低碳基氧基，卤素原子，羟基或与R6形成的亚甲二氧基或与R6形成的异丙亚甲基二氧基; R6代表氢原子，低碳基氧基或与R5形成的亚甲二氧基或与R5形成的异丙亚甲基二氧基; R7代表氢原子或低碳基; R8代表氢原子，羟基，氨基，低碳基羰基氧基或卤素原子。
• PHENANTHROINDOLIZIDINE DERIVATIVE AND NF B INHIBITOR CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：Kabushiki Kaisha Yakult Honsha

  公开号：EP2351753A1

  公开（公告）日：2011-08-03

  A novel compound having an excellent NFκB inhibitory effect is provided. Specifically disclosed is a compound represented by the following formula (1) or a salt thereof: wherein, R1 represents a hydrogen atom, a lower alkyl group, or the like; R2 represents a hydrogen atom, a lower alkyl group, a halogen atom, or the like; R3 represents a hydrogen atom, a lower alkyl group, a hydroxyl group, or a halogen atom; R4 represents a hydrogen atom or a lower alkyloxy group; R5 represents a hydrogen atom, a lower alkyloxy group, a halogen atom, a hydroxyl group, or a methylenedioxy group formed together with R6 or an isopropylidenedioxy group formed together with R6; R6 represents a hydrogen atom, a lower alkyloxy group, or a methylenedioxy group formed together with R5 or an isopropylidenedioxy group formed together with R5; R7 represents a hydrogen atom or a lower alkyl group; and R8 represents a hydrogen atom, a hydroxyl group, an amino group, a lower alkylcarbonyloxy group, or a halogen atom.

  本研究提供了一种具有优异 NFκB 抑制作用的新型化合物。具体公开了由下式（1）代表的化合物或其盐： 其中，R1 代表氢原子、低级烷基或类似物； R2 代表氢原子、低级烷基、卤素原子或类似物； R3 代表氢原子、低级烷基、羟基或卤素原子； R4 代表氢原子或低级烷氧基； R5 代表氢原子、低级烷氧基、卤素原子、羟基或与 R6 共同形成的亚甲基二氧基或与 R6 共同形成的亚异丙基二氧基； R6 代表氢原子、低级烷氧基或与 R5 共同形成的亚甲基二氧基或与 R5 共同形成的亚异丙基二氧基； R7 代表氢原子或低级烷基；以及 R8 代表氢原子、羟基、氨基、低级烷基羰氧基或卤原子。
• PHENANTHROINDOLIZIDINE DERIVATIVE AND NF kB INHIBITOR CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：Kabushiki Kaisha Yakult Honsha

  公开号：EP2351753B1

  公开（公告）日：2015-02-11
• US8569327B2
  申请人：——

  公开号：US8569327B2

  公开（公告）日：2013-10-29
• Synthesis of Phenanthroindolizidine Alkaloids with an Acyloxy Group at the C3 Position and their Antitumor Activities and Toxicities
  作者：Takashi Ikeda、Takashi Yaegashi、Takeshi Matsuzaki、Ryuta Yamazaki、Satoshi Ueno、Syusuke Hashimoto、Seigo Sawada

  DOI：10.2174/157018012800389232

  日期：2012.4.26

  We previously reported that the phenanthroindolizidine alkaloid 3 and its derivatives had markedly potent in vitro cytotoxicity. However, they had low in vivo antitumor activities and high in vivo toxicities, which was a serious problem for further development. Based on the finding that antitumor activity and toxicity could be improved by acetylation of 3, we synthesized new derivatives of 3, which possessed various acyl groups, and evaluated their antitumor activities and toxicities. We found that derivatives with sterically less bulky acyl groups had improved antitumor activities.

  我们之前报告过，苯并吲哚烯醇真碱3及其衍生物在体外具有显著的细胞毒性。然而，它们在体内的抗肿瘤活性较低且毒性较高，这对进一步开发构成了严重问题。基于通过乙酰化3可以改善抗肿瘤活性和毒性的发现，我们合成了3的新衍生物，这些衍生物具有不同的酰基，并评估了它们的抗肿瘤活性和毒性。我们发现，具有立体较小酰基的衍生物的抗肿瘤活性得到了改善。