(3S,12aS)-3-methyl-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino[2',1':6,1]pyrido[3,4-b]indole | 320589-61-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (3S,12aS)-3-methyl-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino[2',1':6,1]pyrido[3,4-b]indole
• 英文别名: (3S,12aS)-3-methyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione；(3S,12aS)-3-methyl-2,3,6,7,12,12a-hexahydropyrazino[1,2-b]β-carboline-1,4-dione；(5S,8S)-5-methyl-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione
• CAS: 320589-61-5
• 化学式: C₁₅H₁₅N₃O₂
• 分子量: 269.303
• InChiKey: YBFSNSRKOIYLIT-SDBXPKJASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  65.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3S,12aS)-3-methyl-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino[2',1':6,1]pyrido[3,4-b]indole 在 sodium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 (1S,12S)-12-methyl-3,11,14,17-tetrazahexacyclo[12.11.0.02,11.04,9.016,24.018,23]pentacosa-2,4,6,8,16(24),18,20,22-octaene-10,13-dione
  参考文献：
  名称：

  The fate of the tryptophan stereocenter in the synthesis of 7,10,16,16a-tetrahydro-11H-quinazolino[2′,3′:3,4]pyrazino[1,2-b]β-carboline-5,8-diones

  摘要：

  Condensation reactions of anthranilic acid with iminoethers 14-17 derived from tetracycles 9-13 to give the title hexacyclic compounds reflect a preferred trans-relationship for H(10)-H(16a) protons in C(7)-unsubstituted products and a cis-relatioship for H(7)-H(16a) protons in C(10)-unsubstituted analogs. This synthetic strategy is limited by the steric hindrance of the substituent at C(10). Theoretical calculations are in agreement with the experimental results. The regioselectivity in favor of the linear tetracyclic compound 11 with respect to 12 has also been confirmed. (C) 2000 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0957-4166(00)00282-2
• 作为产物：
  描述：

  (S)-2,3,4,9-四氢-1H-吡啶[3,4-b]吲哚-3-羧酸 在 N-甲基吗啉 、 盐酸 、 sodium hydroxide 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 141.17h， 生成 (3S,12aS)-3-methyl-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino[2',1':6,1]pyrido[3,4-b]indole
  参考文献：
  名称：

  Toward breast cancer resistance protein (BCRP) inhibitors: design, synthesis of a series of new simplified fumitremorgin C analogues

  摘要：

  In this study, we report the design and synthesis of a series of new simplified fumitremorgin C analogues. The preliminary biological study indicated some of these simplified fumitremorgin C might be developed into breast cancer resistance inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2007.04.045

文献信息

• Microwave assisted stereospecific synthesis of (S)-3-substituted 2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-diones
  作者：Suresh K Pandey、Keshav K Awasthi、Anil K Saxena

  DOI：10.1016/s0040-4020(01)00334-9

  日期：2001.5

  A new easy way of preparing (S)-3-substituted 2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-diones, an important intermediate compound, is described using microwave irradiation supported on silica gel. The reaction is generalised and good to excellent yields of enantiomerically pure products are obtained.

  一种制备（S）-3-取代的2,3,6,7,12,12a-六氢吡嗪并[1'，2'：1,6]吡啶[3,4- b ]吲哚-1,4的简便方法使用载于硅胶上的微波辐射描述了重要的中间体化合物-二酮。反应被普遍进行，并且获得对映体纯产物的良好至极好的收率。
• A new class of anti-thrombosis hexahydropyrazino-[1′,2′:1,6]pyrido-[3,4-b]-indole-1,4-dions: Design, synthesis, logK determination, and QSAR analysis
  作者：Jiawang Liu、Guofeng Wu、Guohui Cui、Wei-Xuan Wang、Ming Zhao、Chao Wang、Ziding Zhang、Shiqi Peng

  DOI：10.1016/j.bmc.2007.06.012

  日期：2007.9.1

  (tetrahydro-beta-carboline-3-carboxy-l-amino acid benzylesters, 2-aminoacyltetrahydro-beta-carboline-3-carboxylic acid benzylesters) were prepared and used for the cyclization to form 5a-t. Coupling hydrochloric acid salt of tetrahydro-beta-carboline-3-carboxylic acid esters and Boc-amino acids in the reported literature usually generates very low yield products accompanied by racemization. However, in our case, the

  基于N-[（3S）]-1,2,3,4-四氢-β-咔啉-3-羧基] -1-赖氨酸在乙酸水溶液（5％）和大鼠中的环化血浆给出了相同的产物，并假设环化产物具有抗血栓活性，我们报道了20种六氢吡嗪并[1'，2'：1,6]吡啶并[ 3,4-b]吲哚-1,4-dion（5a-t）作为潜在的抗血栓形成剂。制备了两种中间体（四氢-β-咔啉-3-羧基-1-氨基酸苄酯，2-氨基酰基四氢-β-咔啉-3-羧酸苄酯），并用于环化形成5a-t。在已报道的文献中，四氢-β-咔啉-3-羧酸酯的盐酸盐与Boc-氨基酸的偶联通常产生非常低的收率产物，并伴随着消旋作用。然而，在我们的情况下，四氢-β-咔啉-3-羧酸苄酯的游离碱以高收率且没有外消旋作用产生了所需的产物。来自体外和体内研究的抗血栓形成结果表明，5a-t可能是一类新型的抗血栓形成剂，口服有效有效浓度为0.5μmol/ kg。此外，使用e-dragon服务器生成的分子
• A Class of 3<i>S</i>-2-Aminoacyltetrahydro-β-carboline-3-carboxylic Acids: Their Facile Synthesis, Inhibition for Platelet Activation, and High in Vivo Anti-Thrombotic Potency
  作者：Jiawang Liu、Xueyun Jiang、Ming Zhao、Xiaoyi Zhang、Meiqing Zheng、Li Peng、Shiqi Peng

  DOI：10.1021/jm901816j

  日期：2010.4.22

  3S-Tetrahydro-beta-carboline-3-carboxylic acid (TCCA) effectively inhibits ADP-induced platelet activation. This paper used TCCA as a lead, modified its 2-position with amino acids, and provided 20 novel 3S-2-aminoacyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acids (5a-t). With the in vitro assay, it was demonstrated that this modification diminished the IC(50) values from 701 nM of TCCA to 10 nM of 5a-t. With the in vivo assay, it was demonstrated that this modification reduced the efficacious dose from 5.0 mu mol/kg of TCCA to 0.1 mu mol/kg of 5a-t. Comparing the Cerius(2) based conformation of them with that of their analogues, the 3-position modified TCCA, it was suggested that the comparatively unfolded conformation was one of the important factors of enhancing the in vivo antithrombotic potency.