1R,3R-1-(3,5-dimethoxy-4-hydroxyphenyl)-3-hydroxymethyl-1,2,3,4-tetrahydro-β-carboline | 157636-87-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: 1R,3R-1-(3,5-dimethoxy-4-hydroxyphenyl)-3-hydroxymethyl-1,2,3,4-tetrahydro-β-carboline
• 英文别名: 4-[(1R,3R)-3-(hydroxymethyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl]-2,6-dimethoxyphenol
• CAS: 157636-87-8
• 化学式: C₂₀H₂₂N₂O₄
• 分子量: 354.406
• InChiKey: AFBWTWVJZLVTSS-KZULUSFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  86.7
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N,N'-羰基二咪唑 、 1R,3R-1-(3,5-dimethoxy-4-hydroxyphenyl)-3-hydroxymethyl-1,2,3,4-tetrahydro-β-carboline 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 (3aR,10R)-10-(4-Hydroxy-3,5-dimethoxy-phenyl)-3a,4,9,10-tetrahydro-3H-2-oxa-9,10a-diaza-cyclopenta[b]fluoren-1-one
  参考文献：
  名称：

  Structure-activity relationship for DNA topoisomerase II-induced DNA cleavage by azatoxin analogues

  摘要：

  Eighteen analogues of the nonintercalative DNA topoisomerase II (topo II)-active epipodophyllotoxin-ellipticine hybrid, azatoxin, were synthesized and evaluated for their ability to induce topo II-mediated DNA strand breaks in vitro. In general, the SAR profile of the azatoxins showed more homology with that of the epipodophyllotoxins than with the ellipticines. Of the compounds studied, only fluoro substitution at the 8-, 9, and 10-positions of azatoxins enhanced activity, with 9-fluoroazatoxin being the most active compound in this series. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00113-2
• 作为产物：
  描述：

  D-色氨酸甲酯 在 sodium tetrahydroborate 、 sodium sulfate 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 苯 为溶剂， 反应 75.0h， 生成 1R,3R-1-(3,5-dimethoxy-4-hydroxyphenyl)-3-hydroxymethyl-1,2,3,4-tetrahydro-β-carboline
  参考文献：
  名称：

  Structure-activity relationship for DNA topoisomerase II-induced DNA cleavage by azatoxin analogues

  摘要：

  Eighteen analogues of the nonintercalative DNA topoisomerase II (topo II)-active epipodophyllotoxin-ellipticine hybrid, azatoxin, were synthesized and evaluated for their ability to induce topo II-mediated DNA strand breaks in vitro. In general, the SAR profile of the azatoxins showed more homology with that of the epipodophyllotoxins than with the ellipticines. Of the compounds studied, only fluoro substitution at the 8-, 9, and 10-positions of azatoxins enhanced activity, with 9-fluoroazatoxin being the most active compound in this series. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00113-2

文献信息

• US5606060A
  申请人：——

  公开号：US5606060A

  公开（公告）日：1997-02-25
• US5747520A
  申请人：——

  公开号：US5747520A

  公开（公告）日：1998-05-05
• [EN] TOPOISOMERASE II INHIBITORS AND THERAPEUTIC USES THEREFOR<br/>[FR] INHIBITEURS DE LA TOPO-ISOMERASE II ET LEURS UTILISATIONS THERAPEUTIQUES
  申请人：THE UNITED STATES OF AMERICA, as represented by THE SECRETARY OF HEALTH AND HUMAN SERVICES

  公开号：WO1994010175A1

  公开（公告）日：1994-05-11

  (EN) Azatoxin and derivatives thereof of formulae B-D are illustrative of a new class of antitumor drugs that are topoisomerase II (top 2) inhibitors. The pharmacophore inhibits the catalytic activity of the purified enzyme but does not unwind relaxed or supercoiled DNA. It is nonintercalative and has at least two domains: a quasi-planar polycyclic ring system, which may bind between DNA base pairs, and a pendant substituent thought to interact with the enzyme, with the DNA grooves or with both. In SV40 and C-myc DNA, azatoxin induces numerous double-strand breaks according to a cleavage pattern which differs from those of known top (2) inhibitors. Azatoxin also is a potent inhibitor of tubulin polymerization.(FR) L'azatoxine et ses dérivés des formules B à D illustrent une nouvelle classe de médicaments antitumoraux qui sont des inhibiteurs de la topo-isomérase II (top 2). Le pharmacophore inhibe l'activité catalytique de l'enzyme purifiée, mais ne déroule pas l'ADN relâché ou superhélixe. Il est non intercalaire et possède au moins deux domaines: un système d'anneau polycyclique quasi plan qui peut se fixer entre les paires de base d'ADN, et un substituant pendant supposé avoir une interaction avec l'enzyme, avec les sillons d'ADN ou avec les deux. Dans l'ADN SV40 et l'ADN C-myc, l'azatoxine induit de nombreuses ruptures double brin selon un modèle de clivage qui diffère de ceux des inhibiteurs connus de la top 2. L'azatoxine est également un puissant inhibiteur de la polymérisation de la tubuline.
• Structure-activity relationship for DNA topoisomerase II-induced DNA cleavage by azatoxin analogues
  作者：Jose S. Madalengoitia、Jetze J. Tepe、Karl A. Werbovetz、Erich K. Lehnert、Timothy L. Macdonald

  DOI：10.1016/s0968-0896(97)00113-2

  日期：1997.9

  Eighteen analogues of the nonintercalative DNA topoisomerase II (topo II)-active epipodophyllotoxin-ellipticine hybrid, azatoxin, were synthesized and evaluated for their ability to induce topo II-mediated DNA strand breaks in vitro. In general, the SAR profile of the azatoxins showed more homology with that of the epipodophyllotoxins than with the ellipticines. Of the compounds studied, only fluoro substitution at the 8-, 9, and 10-positions of azatoxins enhanced activity, with 9-fluoroazatoxin being the most active compound in this series. (C) 1997 Elsevier Science Ltd.