methyl (3S,1R)-1-[3,5-dimethoxy-4-(phenylmethoxy)phenyl]-1,2,3,4-tetrahydro-β-carboline-3-carboxylate | 352015-84-0

• 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: methyl (3S,1R)-1-[3,5-dimethoxy-4-(phenylmethoxy)phenyl]-1,2,3,4-tetrahydro-β-carboline-3-carboxylate
• 英文别名: methyl (1R,3S)-1-(3,5-dimethoxy-4-phenylmethoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 352015-84-0
• 化学式: C₂₈H₂₈N₂O₅
• 分子量: 472.541
• InChiKey: RVGIFJRJUHCQQM-WIOPSUGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  81.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (3S,1R)-1-[3,5-dimethoxy-4-(phenylmethoxy)phenyl]-1,2,3,4-tetrahydro-β-carboline-3-carboxylate 在 lithium hydroxide 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (R)-2-{[(1R,3S)-1-(4-Benzyloxy-3,5-dimethoxy-phenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carbonyl]-amino}-3-phenyl-propionic acid methyl ester
  参考文献：
  名称：

  The synthesis of amino-acid functionalized β-Carbolines as topoisomerase II inhibitors

  摘要：

  The synthesis and biological activity of amino acid functionalized beta -carboline derivatives, which are structurally related to azatoxin and the tryprostatins, are reported. These compounds were assayed for their growth inhibition properties in H520 and PC3 cell lines and were examined for their abilities to inhibit topoisomerase II-mediated DNA relaxation. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00136-6
• 作为产物：
  描述：

  4-苄氧基-3,5-二甲氧基苯甲醛 、 L-色氨酸甲酯 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 20.0h， 生成 methyl (3S,1R)-1-[3,5-dimethoxy-4-(phenylmethoxy)phenyl]-1,2,3,4-tetrahydro-β-carboline-3-carboxylate
  参考文献：
  名称：

  The synthesis of amino-acid functionalized β-Carbolines as topoisomerase II inhibitors

  摘要：

  The synthesis and biological activity of amino acid functionalized beta -carboline derivatives, which are structurally related to azatoxin and the tryprostatins, are reported. These compounds were assayed for their growth inhibition properties in H520 and PC3 cell lines and were examined for their abilities to inhibit topoisomerase II-mediated DNA relaxation. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00136-6

文献信息

• Synthesis of diketopiperazine-based carboline homodimers and in vitro growth inhibition of human carcinomas
  作者：Amy M. Deveau、Nancy E. Costa、Elizabeth M. Joshi、Timothy L. Macdonald

  DOI：10.1016/j.bmcl.2008.05.022

  日期：2008.6

  Starting from D-or L-tryptophan, we have synthesized and characterized six compounds 2.29-2.31a and b that belong to a class of nitrogen heterocycles: the carboline-based homodimers. Each individual homodimer features a 1,3-trans relationship on each side of the central diketopiperazine core, but differs in absolute stereochemistry and also in substitution on the 40 and 400 oxygens (-Bn, -CH(3), or -H). The in vitro cytotoxicity of the six compounds was evaluated by measuring the growth inhibition in NCI-H520 and PC-3 human carcinoma cells. Phenol 2.30a inhibited cancer cell growth approximately three times better than its enantiomer 2.30b and possessed a GI(50) comparable to the clinically used agent etoposide in both cell lines. We have concluded that both the stereochemistry imparted by L-tryptophan and the presence of hydroxy substituents at the 40 and 400 positions are necessary to generate cytotoxic properties in the homodimer class. We are now employing 2.30a as a new lead compound in our efforts to discover improved indole-based cancer chemotherapeutics. (C) 2008 Elsevier Ltd. All rights reserved.