methyl (1R,3R)-1-(4-hydroxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate | 1158945-68-6

• 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: methyl (1R,3R)-1-(4-hydroxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 1158945-68-6
• 化学式: C₁₉H₁₈N₂O₃
• 分子量: 322.364
• InChiKey: IRELGTNBKRWOMX-IAGOWNOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  74.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (1R,3R)-1-(4-hydroxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate 在 磺酰氯 作用下， 生成
  参考文献：
  名称：

  一种他达拉非的合成方法

  摘要：

  发明涉及了一种他达拉非的合成方法，具有以下步骤：1）以对羟基苯甲醛作为原料进行缩合反应得到中间体V，2）中间体V氯代得到中间体IV，3）中间体IV与甲醛溶液反应得到中间体III，4）中间体III与氯乙酰氯缩合得到中间体II，5）中间体II与甲胺溶液反应得到他达拉非（I）。该合成方法避免了易制毒管控原料胡椒醛及其衍生化合物或其他价格昂贵原料的使用，本发明为首次报道，本发明提出的制备方法具有原料易得，成本低廉，方法简单，操作方便，产品纯度高，适合工业化生产等特点，可应用于他达拉非的生产。

  公开号：

  CN116063303A
• 作为产物：
  描述：

  methyl (1R,3R)-1-(4-hydroxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate hydrochloride 在 potassium carbonate 作用下， 以 水 、 乙酸乙酯 为溶剂， 生成 methyl (1R,3R)-1-(4-hydroxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
  参考文献：
  名称：

  Syntheses of chiral 1,3-disubstituted tetrahydro-β-carbolines via CIAT process: highly stereoselective Pictet–Spengler reaction of d-tryptophan ester hydrochlorides with various aldehydes

  摘要：

  A highly stereoselective Pictet-Spengler reaction of D-tryptophan methyl ester hydrochloride 1-HCl with various aldehydes via a CIAT (crystallization-induced asymmetric transformation) process is described. It was revealed that the CIAT process should be performed in a mixed solvent of nitromethane and toluene, and a fine tuning of the ratio of nitromethane and toluene for each epimer Mixture of 2-HCl was necessary in order to get as high yields and stereoselectivities as possible. Enantiomerically pure cis (or trans) 1,3-disubstituted tetrahydro-beta-carbolines 2a-2v were obtained by recrystallization or flash chromatography after neutralization of the corresponding hydrochloride salts cis-2-HCl or trans-2-HCl. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2009.01.026

文献信息

• Discovery of novel phosphatidylcholine-specific phospholipase C drug-like inhibitors as potential anticancer agents
  作者：Chatchakorn Eurtivong、Lisa I. Pilkington、Michelle van Rensburg、Reuben M. White、Harpreet Kaur Brar、Shaun Rees、Emily K. Paulin、Chris Sun Xu、Nabangshu Sharma、Ivanhoe K.H. Leung、Euphemia Leung、David Barker、Jóhannes Reynisson

  DOI：10.1016/j.ejmech.2019.111919

  日期：2020.2

  Phosphatidylcholine-specific phospholipase C (PC-PLC) is a promising target for new anticancer treatment. Herein, we report our work in the discovery of novel drug-like PC-PLC inhibitors. Virtual screening led to the identification of promising hits from four different structural series that contain the molecular scaffold of benzenesulphonamides (10), pyrido[3,4-b]indoles (22), morpholinobenzoic acid (84) and benzamidobenzoic acid (80). 164 structural analogues were tested to investigate the chemical space around the hit series and to generate preliminary structurally activity relationships (SAR). Two of the pyrido[3,4-b]indoles (22_10 and 22_15) had comparable or better potency as D609, an established but non-drug-like PC-PLC inhibitor. Furthermore, three morpholinobenzoic acids (84, 84_4 and 84_5) had superior potency than D609. Therefore, this study paves the way towards the development of drug-like PL-PLC inhibitors as potential anticancer agents. (C) 2019 Elsevier Masson SAS. All rights reserved.
• US9573956B2
  申请人：——

  公开号：US9573956B2

  公开（公告）日：2017-02-21