3-O-desmethyl-13a-(R)-deoxytylophorinine | 1223487-86-2

• 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: 3-O-desmethyl-13a-(R)-deoxytylophorinine
• 英文别名: (R)-6,7-dimethoxy-9,10,11,12,12a,13-hexahydro-9a-aza-cyclopenta[b]triphenylene-3-ol；(13aR)-6,7-dimethoxy-9,11,12,13,13a,14-hexahydrophenanthro[9,10-f]indolizin-3-ol
• CAS: 1223487-86-2
• 化学式: C₂₂H₂₃NO₃
• 分子量: 349.43
• InChiKey: DSYIHAGYTDJTNX-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  41.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-hydroxy-6,7-dimethoxy-9-phenanthrenecarboxylic acid methyl ester 在 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 草酰氯 、 palladium 10% on activated carbon 、 水 、 氢气 、 potassium carbonate 、 三氟乙酸 、 sodium iodide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 70.0 ℃ 、101.33 kPa 条件下， 反应 42.75h， 生成 3-O-desmethyl-13a-(R)-deoxytylophorinine
  参考文献：
  名称：

  Stereospecific Synthesis and Biological Evaluation of Monodesmethyl Metabolites of (+)-13a-(S)-Deoxytylophorinine as Potential Antitumor Agents

  摘要：

  Three major monodesmethyl metabolites of (+)-13a-(S)-deoxytylophorinine were synthesized stereospecifically and their configurations at C-13a were determined. Biological assays revealed that one of the metabolites, 3-O-desmethyl-13a-(S)-deoxytylophorinine, had a higher cytotoxic potency than the parent compound or the positive controls doxorubicin (Adriamycin) and paclitaxel (Taxol).

  DOI：

  10.1055/s-0032-1316810

文献信息

• Synthesis of phenanthroindolizidine alkaloids and evaluation of their antitumor activities and toxicities
  作者：Takashi Ikeda、Takashi Yaegashi、Takeshi Matsuzaki、Ryuta Yamazaki、Syusuke Hashimoto、Seigo Sawada

  DOI：10.1016/j.bmcl.2011.07.120

  日期：2011.10

  We previously reported that 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. To address this problem, new phenanthroindolizidine derivatives were synthesized and their antitumor activities and toxicities were evaluated. This study describes the

  我们先前曾报道过菲咯啉吲哚生物碱3及其衍生物在体外具有明显的细胞毒性。然而，它们具有低的体内抗肿瘤活性和高的体内毒性，这是一个严重的问题。为了解决这个问题，合成了新的菲咯啉吲哚衍生物，并评估了它们的抗肿瘤活性和毒性。这项研究描述了这些菲咯啉吲哚并咪唑衍生物的化学结构，抗肿瘤活性和毒性之间的关系。基于其性质，发现化合物8是最合适的潜在抗肿瘤剂。
• 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 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）。
• PHENANTHROINDOLIZIDINE COMPOUND AND NF kB INHIBITOR CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：Kabushiki Kaisha Yakult Honsha

  公开号：EP2351754B1

  公开（公告）日：2015-06-24
• METHODS AND PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF INFLAMMATORY SKIN DISEASES ASSOCIATED WITH DESMOGLEIN-1 DEFICIENCY
  申请人：INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA MÉDICALE)

  公开号：US20190125826A1

  公开（公告）日：2019-05-02

  The present invention relates to methods and pharmaceutical composition for the treatment of inflammatory skin diseases associated with desmoglein-1 deficiency. The inventors show, for the first time, that the structural protein DSG1 directly acts as a novel and unexpected inhibitor of epithelial inflammation via the inhibition of NF-κB signaling pathway. In particular, the present invention relates to a method of treating an inflammatory skin disease associated with desmoglein-1 deficiency in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an agent capable of restoring the expression of desmogelin-1. Particularly, the inventors carried out the whole exome sequencing, histopathological, electron microscopy, immunofluorescence and immunological analyses in two unrelated patients presenting with SAMEC syndrome.