methyl (1S,3R)-1-(3-hydroxy-4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate

• 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 (1S,3R)-1-(3-hydroxy-4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• 英文别名: (1S,3R)-1-(3-hydroxy-4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester
• 化学式: C₂₀H₂₀N₂O₄
• 分子量: 352.39
• InChiKey: XXQPNGWFNGRDEE-QAPCUYQASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.66
• 重原子数：
  26.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  83.58
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  异香兰素 、 D-色氨酸甲酯盐酸盐 在 三氟乙酸 作用下， 以 水 为溶剂， 反应 12.0h， 以11.111%的产率得到
  参考文献：
  名称：

  Discovery of novel phosphatidylcholine-specific phospholipase C drug-like inhibitors as potential anticancer agents

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2019.111919

文献信息

• Drug-to-Genome-to-Drug, Step 2: Reversing Selectivity in a Series of Antiplasmodial Compounds
  作者：Terence B. Beghyn、Julie Charton、Florence Leroux、Antoine Henninot、Irena Reboule、Paul Cos、Louis Maes、Benoit Deprez

  DOI：10.1021/jm201422e

  日期：2012.2.9

  In a recent paper, we have described the discovery of antimalarial compounds derived from tadalafil, using a drug-to-genome-to-drug approach (J. Med. Chem. 2011, 54 (9), pp 3222-3240). We have shown that these derivatives inhibit the phosphodiesterase activity of Plasmodium falciparum and the parasite growth in culture. In this paper, we describe the optimization of these compounds. A direct consequence of our approach based on gene orthology is the lack of selectivity of the compounds over the original activity on the human target. We demonstrate here that it is possible to take advantage of subtle differences in SAR between HsPDE5 inhibition and antiplasmodial activity to improve significantly the selectivity. In particular, the replacement of the piperonyl group in compound 2 by a dimethozyphenyl group was the best way to optimize selectivity. This observation is consistent with the differences between human and plasmodial sequences in the Q2 pocket receiving this group.