N-{2-[3-(Morpholine-4-carbonyl)-9H-β-carbolin-1-yl]-5,8-dioxo-5,8-dihydro-quinolin-7-yl}-acetamide | 872452-50-1

• 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: N-{2-[3-(Morpholine-4-carbonyl)-9H-β-carbolin-1-yl]-5,8-dioxo-5,8-dihydro-quinolin-7-yl}-acetamide
• 英文别名: 7-N-acetyldemethyllavendamycin morpholine amide；N-[2-[3-(morpholine-4-carbonyl)-9H-pyrido[3,4-b]indol-1-yl]-5,8-dioxoquinolin-7-yl]acetamide
• CAS: 872452-50-1
• 化学式: C₂₇H₂₁N₅O₅
• 分子量: 495.494
• InChiKey: QJPPJOZNGJONGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  37
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-{2-[3-(Morpholine-4-carbonyl)-9H-β-carbolin-1-yl]-5,8-dioxo-5,8-dihydro-quinolin-7-yl}-acetamide 在 硫酸 、 水 、 sodium carbonate 作用下， 以 水 为溶剂， 以63%的产率得到demethyllavendamycin morpholine amide
  参考文献：
  名称：

  Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin antitumor agents

  摘要：

  A series of lavendamycin analogues with two, three or four substituents at the C-6, C-7 N, C-2', C-3' and C-11' positions were synthesized via short and efficient methods and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. The compounds were prepared through Pictet-Spengler condensation of the desired 2-formylquinoline-5,8-diones with the required tryptophans followed by further needed transformations. Metabolism and toxicity studies demonstrated that the best substrates for NQO1 were also the most selectively toxic to NQO1-rich tumor cells compared to NQO1-deficient tumor cells. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.01.037
• 作为产物：
  描述：

  3-[2-Amino-2-(2,5-dioxo-pyrrolidin-1-yloxycarbonyl)-ethyl]-indole-1-carboxylic acid benzyl ester 在 palladium on activated charcoal ammonium formate 、 三乙胺 作用下， 以 乙醇 、 氯仿 、 苯甲醚 为溶剂， 反应 19.5h， 生成 N-{2-[3-(Morpholine-4-carbonyl)-9H-β-carbolin-1-yl]-5,8-dioxo-5,8-dihydro-quinolin-7-yl}-acetamide
  参考文献：
  名称：

  新型拉文达霉素类似物作为抗肿瘤剂：使用NAD（P）H：醌氧化还原酶1的合成，体外细胞毒性，结构代谢和计算机分子建模研究。

  摘要：

  合成了具有各种取代基的新型拉文霉素类似物，并将其评估为潜在的NAD（P）H：醌氧化还原酶（NQO1）定向的抗肿瘤药。喹啉或喹诺啉5,8-二酮醛与色胺或色氨酸的Pictet-Spengler缩合产生拉文霉素。重组人NQO1的代谢研究表明，在喹啉二酮7位和吲哚吡啶2'位添加NH2和CH2OH基团对底物特异性具有最大的积极影响。最好和最差的底物是37（2'-CH2OH-7-NH2衍生物）和31（2'-CONH2-7-NHCOC3H7-n衍生物），还原速率分别为263 +/- 30和0.1 +/- 0.1 micromol /最小/毫克NQO1。确定了拉文霉素对人结肠腺癌细胞的细胞毒性。与缺乏NQO1的BE-WT细胞相比，NQO1的最佳底物对富含NQO1的BE-NQ细胞的毒性也最强，选择性为37。分子对接支持了一种模型，其中最佳的底物能够与活性位点的关键残基进行有效的氢键相互作用，以及氢化物离子的接收。

  DOI：

  10.1021/jm050758z

文献信息

• Novel Lavendamycin Analogues as Antitumor Agents:  Synthesis, in Vitro Cytotoxicity, Structure−Metabolism, and Computational Molecular Modeling Studies with NAD(P)H:Quinone Oxidoreductase 1
  作者：Mary Hassani、Wen Cai、David C. Holley、Jayana P. Lineswala、Babu R. Maharjan、G. Reza Ebrahimian、Hassan Seradj、Mark G. Stocksdale、Farahnaz Mohammadi、Christopher C. Marvin、John M. Gerdes、Howard D. Beall、Mohammad Behforouz

  DOI：10.1021/jm050758z

  日期：2005.12.1

  lavendamycin analogues with various substituents were synthesized and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. Pictet-Spengler condensation of quinoline- or quninoline-5,8-dione aldehydes with tryptamine or tryptophans yielded the lavendamycins. Metabolism studies with recombinant human NQO1 revealed that addition of NH2 and CH2OH groups at the quinolinedione-7-position

  合成了具有各种取代基的新型拉文霉素类似物，并将其评估为潜在的NAD（P）H：醌氧化还原酶（NQO1）定向的抗肿瘤药。喹啉或喹诺啉5,8-二酮醛与色胺或色氨酸的Pictet-Spengler缩合产生拉文霉素。重组人NQO1的代谢研究表明，在喹啉二酮7位和吲哚吡啶2'位添加NH2和CH2OH基团对底物特异性具有最大的积极影响。最好和最差的底物是37（2'-CH2OH-7-NH2衍生物）和31（2'-CONH2-7-NHCOC3H7-n衍生物），还原速率分别为263 +/- 30和0.1 +/- 0.1 micromol /最小/毫克NQO1。确定了拉文霉素对人结肠腺癌细胞的细胞毒性。与缺乏NQO1的BE-WT细胞相比，NQO1的最佳底物对富含NQO1的BE-NQ细胞的毒性也最强，选择性为37。分子对接支持了一种模型，其中最佳的底物能够与活性位点的关键残基进行有效的氢键相互作用，以及氢化物离子的接收。
• Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin antitumor agents
  作者：Wen Cai、Mary Hassani、Rajesh Karki、Ervin D. Walter、Katherine H. Koelsch、Hassan Seradj、Jayana P. Lineswala、Hamid Mirzaei、Jeremy S. York、Fatemeh Olang、Minoo Sedighi、Jennifer S. Lucas、Thomas J. Eads、Anthony S. Rose、Sahba Charkhzarrin、Nicholas G. Hermann、Howard D. Beall、Mohammad Behforouz

  DOI：10.1016/j.bmc.2010.01.037

  日期：2010.3

  A series of lavendamycin analogues with two, three or four substituents at the C-6, C-7 N, C-2', C-3' and C-11' positions were synthesized via short and efficient methods and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. The compounds were prepared through Pictet-Spengler condensation of the desired 2-formylquinoline-5,8-diones with the required tryptophans followed by further needed transformations. Metabolism and toxicity studies demonstrated that the best substrates for NQO1 were also the most selectively toxic to NQO1-rich tumor cells compared to NQO1-deficient tumor cells. (C) 2010 Elsevier Ltd. All rights reserved.