(14S)-14-hydroxy-2,3,6,7-tetramethoxyphenanthro<9,10-b>indolizidine | 87302-58-7

• 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: (14S)-14-hydroxy-2,3,6,7-tetramethoxyphenanthro<9,10-b>indolizidine
• 英文别名: (13aS,14S)-14-hydroxyl tylocrebrine；(13aS,14S)-14-hydroxytylophorine；6-O-desmethylcryptopleurine；14-hydroxytylophorine；DCB-3503；NSC-716802；Dibenzo(f,H)pyrrolo(1,2-b)isoquinolin-14-ol, 9,11,12,13,13a,14-hexahydro-2,3,6,7-tetramethoxy-, (13as-trans)-；(13aS,14S)-2,3,6,7-tetramethoxy-9,11,12,13,13a,14-hexahydrophenanthro[9,10-f]indolizin-14-ol
• CAS: 87302-58-7
• 化学式: C₂₄H₂₇NO₅
• 分子量: 409.482
• InChiKey: JWHWLMNMGLICQZ-MHECFPHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  6

制备方法与用途

Tylophorine类似物DCB-3503是一种潜在的抗癌和免疫抑制剂。它通过在延伸步骤中抑制细胞调节蛋白的翻译，特别是细胞周期蛋白D1，发挥其作用。此外，DCB-3503还能变构调节HSC70的ATP酶和伴侣活性，这一过程依赖于细胞周期蛋白D1 mRNA中的特定RNA结合基序（AUUUA）的存在并促进ATP水解。

反应信息

• 作为反应物：
  描述：

  (14S)-14-hydroxy-2,3,6,7-tetramethoxyphenanthro<9,10-b>indolizidine 在 三乙基硅烷 、 三氟乙酸 作用下， 反应 10.0h， 以94%的产率得到(S)-9,11,12,13,13a,14-六氢-2,3,6,7-四甲氧基二苯并[f,h]吡咯并(1,2-b)异喹啉
  参考文献：
  名称：

  Parham型环酰化反应高效、手性特异性合成菲-吲哚里西啶生物碱

  摘要：

  以 Parham 型环酰化为关键步骤的简洁、高效和模块化的路线已被用于合成六种对映体纯的菲-吲哚里西啶生物碱 1a-c。大规模制备对映体纯的泰洛弗拉生物碱及其类似物现在是可行的。醇中间体8a-c难以通过其他合成方法制备，通过金属化-环化-还原序列以优异的产率合成。

  DOI：

  10.1002/ejoc.200900920
• 作为产物：
  描述：

  9-bromo-10-(bromomethyl)-2,3,6,7-tetramethoxyphenanthrene 在 sodium tetrahydroborate 、 正丁基锂 、 四甲基乙二胺 、 水 、 potassium carbonate 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 (14S)-14-hydroxy-2,3,6,7-tetramethoxyphenanthro<9,10-b>indolizidine
  参考文献：
  名称：

  Design, Synthesis, and Anti-tobacco Mosaic Virus (TMV) Activity of Phenanthroindolizidines and Their Analogues

  摘要：

  On the basis of our previous structure-activity relationship (SAR) and antiviral mechanism studies, a series of phenanthroindolizidines and their analogues 3-20 were designed, targeting tobacco mosaic virus (TMV) RNA, synthesized, and systematically evaluated for their antiviral activity against TMV. The bioassay results showed that most of these compounds displayed good anti-TMV activity, and some of them exhibited higher antiviral activity than that of commercial Ningnanmycin (perhaps the most successful registered antiplant viral agent). Especially, (S)-deoxytylophorinine (5) with excellent anti-TMV activity (inactivation activity, 59.8%/500 mu g mL(-1) and 40.3%/100 mu g mL(-1); curative activity, 65.1%/500 mu g mL(-1) and 43.7%/100 mu g mL(-1); and protection activity, 70.2%/500 mu g mL(-1) and 51.3%/100 mu g mL(-1)) emerged as a potential inhibitor of the plant virus. Compound 20 exhibited a strong in vivo protection effect against TMV at 100 mu g mL(-1), which indicated that phenanthroindolizidine analogues with a seven-membered D ring have a new and interesting structural scaffold and have great potential for further development as tobacco protection agents.

  DOI：

  10.1021/jf303550a

文献信息

• 菲并吲哚里西啶生物碱糖基化产物及6-位衍 生化产物及它们的制备、抗植物病毒活性
  申请人：南开大学

  公开号：CN103923134B

  公开（公告）日：2016-11-09

  本发明涉及菲并吲哚里西啶生物碱糖基化产物和6‑位衍生化产物及其制备和抗植物病毒活性，式中各基团的意义见说明书。本发明的菲并吲哚里西啶生物碱糖基化产物具有好的光稳定性，热稳定性和水溶性，表现出特别优异的抗植物病毒活性，糖基化产物和6‑位衍生化产物均能很好地抑制烟草花叶病毒(TMV)。
• Design, Synthesis, and &lt;i&gt;in Vitro&lt;/i&gt; Biological Evaluation of 14-Hydroxytylophorine-dichloroacetate Co-drugs as Antiproliferative Agents
  作者：Ziad Omran、Mohamed Alarja、Ashraf N. Abdalla、Munjed M. Ibrahim、Mohammad A. Hossain、Linwei Chen、Yuxiu Liu、Qingmin Wang

  DOI：10.1248/cpb.c19-00520

  日期：2019.11.1

  Co-drug, or mutual-prodrug, is a drug design approach consisting of covalently linking two active drugs so as to improve the pharmacokinetics and/or pharmacodynamics properties of one or both drugs. Co-drug strategy has proven good success in overcoming undesirable properties such as absorption, poor bioavailability, nonspecificity, and gastrointestine tract (GIT) side effects. In this work, we successfully

  共同药物或共同药物是一种药物设计方法，由共价连接两种活性药物组成，以改善一种或两种药物的药代动力学和/或药效学性质。在克服不良特性（例如吸收，不良的生物利用度，非特异性和胃肠道（GIT）副作用）方面，共同药物策略已被证明是成功的。在这项工作中，我们成功开发了14-羟基酪氨酸（一种具有显着抗增殖活性的菲硫吲哚衍生物）和一种已知的丙酮酸脱氢酶激酶抑制剂二氯乙酸盐的共用药物。二氯乙酸盐可引导肿瘤细胞的代谢从糖酵解转变为葡萄糖氧化，进而逆转Warburg效应并使肿瘤细胞具有增殖不利条件。所获得的共同药物保留了14-羟基酪氨酸的细胞毒性。但是，它们对正常细胞显示出类似的非选择性。
• PHENANTHROINDOLIZIDINE COMPOUND AND NFkB INHIBITOR CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：Ikeda Takashi

  公开号：US20110201638A1

  公开（公告）日：2011-08-18

  A novel compound having an excellent NFκB inhibitory effect is provided and 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, a lower alkyloxy group, or a halogen atom; R 2 represents a hydroxyl group, or a lower alkyloxy group; R 3 represents a hydrogen atom, a lower alkyl 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, or a lower alkylcarbonyloxy group (excluding the case where R 1 , R 3 , R 4 and R 7 are hydrogen atoms, R 2 and R 8 are hydroxyl groups, and R 5 and R 6 are methoxy groups).

  提供了一种具有优异NFκB抑制作用的新化合物，具体披露了以下式（1）或其盐的化合物：其中，R1代表氢原子、低级烷基基团、低级烷氧基团或卤素原子；R2代表羟基或低级烷氧基团；R3代表氢原子、低级烷基基团或卤素原子；R4代表氢原子或低级烷氧基团；R5代表氢原子、低级烷氧基团、卤素原子、羟基或与R6形成的亚甲二氧基基团或与R6形成的异丙亚甲二氧基基团；R6代表氢原子、低级烷氧基团或与R5形成的亚甲二氧基基团或与R5形成的异丙亚甲二氧基基团；R7代表氢原子或低级烷基基团；R8代表氢原子、羟基、氨基或低级烷基羧酸酯基团（不包括R1、R3、R4和R7为氢原子，R2和R8为羟基，R5和R6为甲氧基团的情况）。
• 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 COMPOUND AND NF B INHIBITOR CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：Kabushiki Kaisha Yakult Honsha

  公开号：EP2351754A1

  公开（公告）日：2011-08-03

  A novel compound having an excellent NFκB inhibitory effect is provided and 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, a lower alkyloxy group, or a halogen atom; R2 represents a hydroxyl group, or a lower alkyloky group; R3 represents a hydrogen atom, a lower alkyl 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, or a lower alkylcarbonyloxy group (excluding the case where R1, R3, R4 and R7 are hydrogen atoms, R2 and R8 are hydroxyl groups, and R5 and R6 are methoxy groups).

  本发明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) 表示的化合物或其盐： 其中，R1 代表氢原子、低级烷基、低级烷氧基或卤原子； R2 代表羟基或低级烷基； R3 代表氢原子、低级烷基或卤素原子； 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、氨基或低级烷基羰氧基（不包括 R1、R3、R4 和 R7 为氢原子，R2 和 R8 为羟基，R5 和 R6 为甲氧基的情况）。