N-[(3S)-N-Boc-1,2,3,4-tetrahydro-β-carboline-3-carboxyl]glycine benzyl ester | 945650-54-4

• 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: N-[(3S)-N-Boc-1,2,3,4-tetrahydro-β-carboline-3-carboxyl]glycine benzyl ester
• CAS: 945650-54-4
• 化学式: C₂₆H₂₉N₃O₅
• 分子量: 463.533
• InChiKey: KXDLNTRLYQNHCE-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.69
• 重原子数：
  34.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  100.73
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-[(3S)-N-Boc-1,2,3,4-tetrahydro-β-carboline-3-carboxyl]glycine benzyl ester 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 1.17h， 生成
  参考文献：
  名称：

  一类新的抗血栓形成的六氢吡嗪-[1'，2'：1,6]吡啶基-[3,4-b]-吲哚-1,4-dion：设计，合成，logK测定和QSAR分析。

  摘要：

  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

  DOI：

  10.1016/j.bmc.2007.06.012
• 作为产物：
  描述：

  甘氨酸苄酯盐酸盐 、 BOC-L-1,2,3,4-四氢-Β-咔啉-3-羧酸 在 N-甲基吗啉 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以95%的产率得到N-[(3S)-N-Boc-1,2,3,4-tetrahydro-β-carboline-3-carboxyl]glycine benzyl ester
  参考文献：
  名称：

  一类新的抗血栓形成的六氢吡嗪-[1'，2'：1,6]吡啶基-[3,4-b]-吲哚-1,4-dion：设计，合成，logK测定和QSAR分析。

  摘要：

  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

  DOI：

  10.1016/j.bmc.2007.06.012

文献信息

• Dual-acting agents that possess reversing resistance and anticancer activities: Design, synthesis, MES-SA/Dx5 cell assay, and SAR of Benzyl 1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H-imidazo[3′,4′:1,2]pyridin[3,4-b]indol-2-substitutedacetates
  作者：Jiawang Liu、Guohui Cui、Ming Zhao、Chunying Cui、Jingfang Ju、Shiqi Peng

  DOI：10.1016/j.bmc.2007.08.061

  日期：2007.12

  Based on the structural analysis of fumitremorgin C (FTC), imidazoline and beta-carboline amino acid benzylester, 14 novel 2-substitutedtetracyclic derivatives of tetrahydrocarboline 4a-n were prepared. We demonstrated that the exposure of MES-SA/Dx5 cells to some of 4a-n resulted in significant reduction of resistance of the cells against doxorubicin. This reduced resistance was accompanied by lowering of IC50 value to doxorubicin from 1.55 +/- 0.26 mu mol/L to 0.33 +/- 0.05 mu mol/L for 2-(2-butyl)-derivative 4c, to 1.03 +/- 0.22 mu mol/L for 2-methyl-derivative 4d, to 0.46 +/- 0.04 mu mol/L for 2-benzyl-derivative 4f, to 0.98 +/- 0.25 mu mol/L for 2-indole-3-yl-methyl-derivative 4h, to 0.36 +/- 0.03 mu mol/L for 2-benzyloxycarbonylmethyl- derivative 4i, to 0.77 +/- 0.08 mu mol/L for 2-benzyloxycarbonylethyl-derivative 4j, and to 0.77 +/- 0.08 mu mol/L for 2-benzyloxycarbonylamino-n-butyl-derivative 4l. Proliferation assays of 4a-n indicated 4c, f, i, j were able to inhibit the proliferation of doxorubicin resistant MES-SA/Dx5 cells. The SAR analysis revealed that the benzylester form and the tetracyclic structure of 4a-n were critical for both sensitizing doxorubicin and the cellular anti-proliferative effect. (c) 2007 Elsevier Ltd. All rights reserved.
• Benzyl 1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H-imidazo[3′,4′:1,2]pyridin[3,4-b]indole-2-substituted acetates: One-pot-preparation, anti-tumor activity, docking toward DNA and 3D QSAR analysis
  作者：Jiawang Liu、Ming Zhao、Keduo Qian、Xiaoyi Zhang、Kuo-Hsiung Lee、Jianhui Wu、Yi-Nan Liu、Shiqi Peng

  DOI：10.1016/j.bmc.2010.01.038

  日期：2010.3

  To discover the anti-tumoral indoles a series of benzyl 1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H-imidazo[3',4':1,2]pyridin[3,4-b]indole-2-substituted acetates (2a-n) are prepared via one-pot-preparation. The IC50 values of 2a-n in vitro against human lung carcinoma, prostate cancer, nasopharyngeal carcinoma, vincristine-resistant KB subline and human breast carcinoma cells range from 40 nM to 60 mu M. On Sarcoma 180 (S180) tumor-bearing mouse model four of them (2e,g,h,i) significantly inhibited the tumor growth. At the dose of 0.1 mg/kg the efficacy of the most potent 2h was equal to that of 1.0 mg/kg of doxorubicin. In contrast to doxorubicin, at 1.0 mg/kg of dose 2e,g,h,i did not induce the treated S180 mice to have organ atrophy and body emaciation. The healthy mice receiving 10, 100 and 500 mg/kg of 2e,g,h,i gave no any neurotoxic response. Even up to the dose of 500 mg/kg the healthy mice occurred no death. The interaction of 2a-n with DNA was confirmed by the fluorescence quenching experiments and automated flexible ligand docking. By 3D QSAR analysis the IC50 values of 2a-n against prostate cancer cells were correlated with the structures and conformations of their side chains. To increase the data related to their physical-chemical properties the experimental Log P values were also provided. (C) 2010 Elsevier Ltd. All rights reserved.