3S-2-(Boc-L-histidinyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid | 945650-91-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3S-2-(Boc-L-histidinyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid
• 英文别名: (3S)-2-[(2S)-3-(1H-imidazol-5-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylic acid
• CAS: 945650-91-9
• 化学式: C₂₃H₂₇N₅O₅
• 分子量: 453.498
• InChiKey: BRWGVKBIICNPRF-HKUYNNGSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3S-2-(Boc-L-histidinyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 以92%的产率得到3S-2-L-histidinyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid
  参考文献：
  名称：

  A Class of 3S-2-Aminoacyltetrahydro-β-carboline-3-carboxylic Acids: Their Facile Synthesis, Inhibition for Platelet Activation, and High in Vivo Anti-Thrombotic Potency

  摘要：

  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.

  DOI：

  10.1021/jm901816j
• 作为产物：
  描述：

  3S-2-(Boc-L-histidinyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid methyl ester 在 sodium hydroxide 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 1.0h， 以89%的产率得到3S-2-(Boc-L-histidinyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid
  参考文献：
  名称：

  A Class of 3S-2-Aminoacyltetrahydro-β-carboline-3-carboxylic Acids: Their Facile Synthesis, Inhibition for Platelet Activation, and High in Vivo Anti-Thrombotic Potency

  摘要：

  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.

  DOI：

  10.1021/jm901816j

文献信息

• 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.