S-(-)-methyl 2-[N-t-butoxycarbonyl]aminoacetyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate | 354764-97-9

• 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: S-(-)-methyl 2-[N-t-butoxycarbonyl]aminoacetyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate
• 英文别名: (3S)-2-(Boc-glycyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid methyl ester；(S)-methyl 2-(2-((tert-butoxycarbonyl)amino)acetyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate；methyl (3S)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylate
• CAS: 354764-97-9
• 化学式: C₂₀H₂₅N₃O₅
• 分子量: 387.436
• InChiKey: ZNQSDQITOLQABW-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  S-(-)-methyl 2-[N-t-butoxycarbonyl]aminoacetyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate 在 sodium hydroxide 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 1.0h， 以95%的产率得到(3S)-N-(Boc-glycyl)-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：

  (S)-2,3,4,9-四氢-1H-吡啶[3,4-b]吲哚-3-羧酸 在 氯化亚砜 、 2-bromo-1-ethylpyridin-1-ium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 S-(-)-methyl 2-[N-t-butoxycarbonyl]aminoacetyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate
  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

• Exploration of TRPM8 Binding Sites by β-Carboline-Based Antagonists and Their In Vitro Characterization and In Vivo Analgesic Activities
  作者：Alessia Bertamino、Carmine Ostacolo、Alicia Medina、Veronica Di Sarno、Gianluigi Lauro、Tania Ciaglia、Vincenzo Vestuto、Giacomo Pepe、Manuela Giovanna Basilicata、Simona Musella、Gerardina Smaldone、Claudia Cristiano、Sara Gonzalez-Rodriguez、Asia Fernandez-Carvajal、Giuseppe Bifulco、Pietro Campiglia、Isabel Gomez-Monterrey、Roberto Russo

  DOI：10.1021/acs.jmedchem.0c00816

  日期：2020.9.10

  Transient receptor potential melastatin 8 (TRPM8) ion channel represents a valuable pharmacological option for several therapeutic areas. Here, a series of conformationally restricted derivatives of the previously described TRPM8 antagonist N,N′-dibenzyl tryptophan 4 were prepared and characterized in vitro by Ca2+-imaging and patch-clamp electrophysiology assays. Molecular modeling studies led to

  瞬时受体电位褪黑素8（TRPM8）离子通道代表了几个治疗领域的宝贵药理学选择。在此，制备了先前描述的TRPM8拮抗剂N，N′-二苄基色氨酸4的一系列构象受限的衍生物，并通过Ca 2+成像和膜片钳电生理测定体外表征。分子建模研究导致在TRPM8结合位点内确定了这些衍生物的广泛且明确定义的相互作用网络，这是其拮抗剂活性的基础。（5 R，11a S）-5-（4-氯苯基）-2-（4-氟苄基）-5,6,11,11a-四氢-1 H-咪唑[1'，5'：1,6]吡啶[3,4-b ]吲哚-1,3（2 H）-二酮（31a）以有效的（IC 50 = 4.10±1.2 nM），选择性且代谢稳定的TRPM8拮抗剂出现。在体内，31a在icilin诱导的WDS（11.5 mg / kg ip），奥沙利铂诱导的冷异常性疼痛（10-30μgsc）和CCI诱导的热痛觉过敏（11.5 mg / kg）中显示出显着的靶标覆盖范围。
• 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。
• Toward breast cancer resistance protein (BCRP) inhibitors: design, synthesis of a series of new simplified fumitremorgin C analogues
  作者：Guofeng Wu、Jiawang Liu、Lanrong Bi、Ming Zhao、Chao Wang、Michèle Baudy-Floc'h、Jingfang Ju、Shiqi Peng

  DOI：10.1016/j.tet.2007.04.045

  日期：2007.6

  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.
• 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.