3-(6-chloro-2,3,4,4a,9,9a-hexahydro-1H-b-carbolin-1-yl)phenol hydrochloride | 1236397-58-2

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物
• 英文名称: 3-(6-chloro-2,3,4,4a,9,9a-hexahydro-1H-b-carbolin-1-yl)phenol hydrochloride
• 英文别名: 3-(6-chloro-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenol hydrochloride；1-(3-hydroxyphenyl)-6-chloro-1,2,3,4-tetrahydro-β-carboline hydrochloride；3-(6-chloro-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenol;hydrochloride
• CAS: 1236397-58-2
• 化学式: C₁₇H₁₅ClN₂O*ClH
• 分子量: 335.233
• InChiKey: KOKWIYMHTUZOBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.18
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  48
• 氢给体数：
  4
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 3-(6-chloro-2,3,4,4a,9,9a-hexahydro-1H-b-carbolin-1-yl)phenol hydrochloride 在 甲酸 、 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以61.5%的产率得到6-chloro-1-(3-hydroxyphenyl)-2-methyl-1,2,3,4-tetrahydro-β-carboline
  参考文献：
  名称：

  Discovery of tetrahydro-β-carbolines as inhibitors of the mitotic kinesin KSP

  摘要：

  Inhibitors of kinesin spindle protein (KSP) are a promising class of anticancer agents that cause mitotic arrest in cells from a failure to form functional bipolar mitotic spindles. Here, we report the synthesis and biological evaluation of a novel series of tetrahydro-beta-carboline analogs based on the structure of the known KSP inhibitor HR22C16. Preferred compounds 11b, 12a and 19b were identified as potent inhibitors in a KSP ATPase assay with good anti-proliferative activity in A549 cells. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.05.024
• 作为产物：
  描述：

  5-氯-1H-吲哚-3-乙胺盐酸盐 、 间羟基苯甲醛 以 N,N-二甲基甲酰胺 为溶剂， 以14%的产率得到3-(6-chloro-2,3,4,4a,9,9a-hexahydro-1H-b-carbolin-1-yl)phenol hydrochloride
  参考文献：
  名称：

  受杂育亨宾天然产物启发发现高效血清素 5-HT2 受体激动剂

  摘要：

  5-羟色胺 5-HT 2受体是重要的药物靶标，涉及各种神经、精神和心脏功能和功能障碍的信号传导途径。因此，用于研究这些受体活性和下游效应的许多配体已经被合成开发或在自然界中发现。例如，杂育亨宾天然产物alstonine表现出由5-HT 2A/2C激动作用介导的抗精神病活性。在这项工作中，我们鉴定了一种含有血清素药效团的杂育亨宾代谢物，并截短了支架，从而发现了取代的四氢-β-咔啉在 5-HT 2受体家族中的有效激动剂活性。广泛的 SAR 开发导致化合物 106 在 5-HT 2A 、5-HT 2B和 5-HT 2C下的 EC 50值分别为 1.7、0.58 和 0.50 nM。对接研究表明四氢-β-咔啉核心和保守残基色氨酸6.48之间的 π 堆积相互作用是该活性的结构基础。这项工作为未来研究这些化合物在神经和精神疾病中的作用奠定了基础。

  DOI：

  10.1021/acsmedchemlett.1c00694

文献信息

• Antimalarial activity of tetrahydro-β-carbolines targeting the ATP binding pocket of the Plasmodium falciparum heat shock 90 protein
  作者：Scott Eagon、Jared T. Hammill、Jordan Bach、Nikalet Everson、Tyler A. Sisley、Michael J. Walls、Sierra Durham、Dylan R. Pillai、Mofolusho O. Falade、Amy L. Rice、Joshua J. Kimball、Horacio Lazaro、Celine DiBernardo、R. Kiplin Guy

  DOI：10.1016/j.bmcl.2020.127502

  日期：2020.11

  A series of tetrahydro-beta-carboline derivatives of a lead compound known to target the heat shock 90 protein of Plasmodium falciparum were synthesized and assayed for both potency against the parasite and toxicity against a human cell line. Using a rationalized structure based design strategy, a new lead compound with a potency two orders of magnitude greater than the original lead compound was found. Additional modeling of this new lead compound suggests multiple avenues to further increase potency against this target, potentially paving the path for a therapeutic with a mode of action different than any current clinical treatment.
• Discovery of tetrahydro-β-carbolines as inhibitors of the mitotic kinesin KSP
  作者：Fei Liu、Li-Qin Yu、Cheng Jiang、Lei Yang、Wu-Tong Wu、Qi-Dong You

  DOI：10.1016/j.bmc.2010.05.024

  日期：2010.6.15

  Inhibitors of kinesin spindle protein (KSP) are a promising class of anticancer agents that cause mitotic arrest in cells from a failure to form functional bipolar mitotic spindles. Here, we report the synthesis and biological evaluation of a novel series of tetrahydro-beta-carboline analogs based on the structure of the known KSP inhibitor HR22C16. Preferred compounds 11b, 12a and 19b were identified as potent inhibitors in a KSP ATPase assay with good anti-proliferative activity in A549 cells. (C) 2010 Elsevier Ltd. All rights reserved.
• Discovery of Highly Potent Serotonin 5-HT₂ Receptor Agonists Inspired by Heteroyohimbine Natural Products
  作者：Meghan J. Orr、Andrew B. Cao、Charles Tiancheng Wang、Arsen Gaisin、Adam Csakai、Alec P. Friswold、Herbert Y. Meltzer、John D. McCorvy、Karl A. Scheidt

  DOI：10.1021/acsmedchemlett.1c00694

  日期：2022.4.14

  heteroyohimbine natural product alstonine exhibits antispychotic activity mediated by 5-HT2A/2C agonism. In this work, we identified a heteroyohimbine metabolite containing a serotonin pharmacophore and truncated the scaffold, leading to the discovery of potent agonist activity of substituted tetrahydro-β-carbolines across the 5-HT2 receptor family. Extensive SAR development resulted in compound 106 with

  5-羟色胺 5-HT 2受体是重要的药物靶标，涉及各种神经、精神和心脏功能和功能障碍的信号传导途径。因此，用于研究这些受体活性和下游效应的许多配体已经被合成开发或在自然界中发现。例如，杂育亨宾天然产物alstonine表现出由5-HT 2A/2C激动作用介导的抗精神病活性。在这项工作中，我们鉴定了一种含有血清素药效团的杂育亨宾代谢物，并截短了支架，从而发现了取代的四氢-β-咔啉在 5-HT 2受体家族中的有效激动剂活性。广泛的 SAR 开发导致化合物 106 在 5-HT 2A 、5-HT 2B和 5-HT 2C下的 EC 50值分别为 1.7、0.58 和 0.50 nM。对接研究表明四氢-β-咔啉核心和保守残基色氨酸6.48之间的 π 堆积相互作用是该活性的结构基础。这项工作为未来研究这些化合物在神经和精神疾病中的作用奠定了基础。