6,6-二甲基-8-羟基-9-溴-11-氧代-6,11-二氢-5H-苯并[B]咔唑-3-甲腈 | 1256579-06-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 6,6-二甲基-8-羟基-9-溴-11-氧代-6,11-二氢-5H-苯并[B]咔唑-3-甲腈
• 中文别名: 9-溴-6,11-二氢-8-羟基-6,6-二甲基-11-氧代-5H-苯并[b]咔唑-3-甲腈
• 英文名称: 9-bromo-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile
• 英文别名: 9-bromo-8-hydroxy-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile
• CAS: 1256579-06-2
• 化学式: C₁₉H₁₃BrN₂O₂
• 分子量: 381.228
• InChiKey: FTLQDYMGJVZZLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  76.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6,6-二甲基-8-羟基-9-溴-11-氧代-6,11-二氢-5H-苯并[B]咔唑-3-甲腈 在 吡啶 、 sodium cyanoborohydride 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 溶剂黄146 为溶剂， 反应 26.0h， 生成 9-bromo-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile
  参考文献：
  名称：

  9-Substituted 6,6-Dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazoles as Highly Selective and Potent Anaplastic Lymphoma Kinase Inhibitors

  摘要：

  9-Substituted 6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazoles were discovered as highly selective and potent anaplastic lymphoma kinase (ALK) inhibitors by structure-based drug design. The high target selectivity was achieved by introducing a substituent close to the E(0) region of the ATP binding site, which has a unique amino acid sequence. Among the identified inhibitors, compound 13d showed highly selective and potent inhibitory activity against ALK with an IC(50) value of 2.9 nM and strong antiproliferative activity against KARPAS-299 with an IC(50) value of 12.8 nM. The compound also displayed significant antitumor efficacy in an established ALK fusion gene-positive anaplastic large-cell lymphoma (ALCL) xenograft model in mice without body weight loss.

  DOI：

  10.1021/jm200652u
• 作为产物：
  描述：

  6-溴-7-甲氧基-1,1-二甲基-3,4-二氢萘-2(1h)-酮 在 吡啶盐酸盐 、 三氟乙酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 6.5h， 生成 6,6-二甲基-8-羟基-9-溴-11-氧代-6,11-二氢-5H-苯并[B]咔唑-3-甲腈
  参考文献：
  名称：

  9-Substituted 6,6-Dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazoles as Highly Selective and Potent Anaplastic Lymphoma Kinase Inhibitors

  摘要：

  9-Substituted 6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazoles were discovered as highly selective and potent anaplastic lymphoma kinase (ALK) inhibitors by structure-based drug design. The high target selectivity was achieved by introducing a substituent close to the E(0) region of the ATP binding site, which has a unique amino acid sequence. Among the identified inhibitors, compound 13d showed highly selective and potent inhibitory activity against ALK with an IC(50) value of 2.9 nM and strong antiproliferative activity against KARPAS-299 with an IC(50) value of 12.8 nM. The compound also displayed significant antitumor efficacy in an established ALK fusion gene-positive anaplastic large-cell lymphoma (ALCL) xenograft model in mice without body weight loss.

  DOI：

  10.1021/jm200652u

文献信息

• TETRACYCLIC COMPOUND
  申请人：Kinoshita Kazutomo

  公开号：US20120083488A1

  公开（公告）日：2012-04-05

  A compound represented by the general Formula (I) below, or a salt or solvate thereof, which is useful as an ALK inhibitor, and is useful for prophylaxis or treatment of a disease accompanied by abnormality in ALK, for example, cancer, cancer metastasis, depression or cognitive function disorder: (meanings of the symbols that are included in the formula are as given in the specification).

  一种由下面的一般式（I）表示的化合物，或其盐或溶剂化物，可用作ALK抑制剂，对于伴有ALK异常的疾病的预防或治疗是有用的，例如癌症、癌症转移、抑郁症或认知功能障碍（方程式中包含的符号的含义如规范中所述）。
• METHOD FOR PREPARING ALECTINIB
  申请人：SUZHOU MIRACPHARMA TECHNOLPGY CO., LTD.

  公开号：US20170247352A1

  公开（公告）日：2017-08-31

  A method for preparing Alectinib (Alectinib, I), comprising the preparation steps: subjecting 6-cyano-1H-indole-3-carboxylate and 4-ethyl-3-(4-morpholine-4-yl-piperidine-1-yl)-α,α-dimethylbenzyl alcohol to condensation, hydrolyzing and cyclization reaction so as to prepare Alectinib (I). The preparation method has easily available raw materials and a simple process, and is economical and environmentally friendly and suitable for industrial production.

  一种制备阿雷替尼（Alectinib, I）的方法，包括以下制备步骤：将6-氰基-1H-吲哚-3-甲酸酯和4-乙基-3-(4-吗啡啉-4-基哌啶-1-基)-α,α-二甲基苄醇进行缩合、水解和环化反应，以制备阿雷替尼（I）。该制备方法具有原料易得、工艺简单、经济环保且适合工业生产的特点。
• COMPOSITION COMPRISING TETRACYCLIC COMPOUND
  申请人：Furumoto Kentaro

  公开号：US20130143877A1

  公开（公告）日：2013-06-06

  A composition which comprises substance represented by Formula (I), [Meanings of the symbols that are included in the formula are given in the specification as definitions] a pharmaceutically acceptable carrier, and a dissolution aid. is useful for improving solubility, oral absorbability and/or absorbability in blood of a poorly water-soluble or water insoluble tetracyclic compounds having an ALK inhibitory activity that are useful as a prophylactic and/or therapeutic agent for cancer, depression, and cognitive function disorder.

  由公式（I）代表的物质，药用可接受的载体和溶解助剂组成的组合物，可用于改善具有ALK抑制活性的水溶性差或水不溶的四环化合物的溶解度、口服吸收性和/或血液吸收性，这些化合物可用作癌症、抑郁症和认知功能障碍的预防和/或治疗药物。
• [EN] A PROCESS FOR PREPARING ALECTINIB OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION D'ALECTINIB OU D'UN SEL PHARMACEUTIQUEMENT ACCEPTABLE DE CELUI-CI
  申请人：FRESENIUS KABI ONCOLOGY LTD

  公开号：WO2019008520A1

  公开（公告）日：2019-01-10

  The present invention relates to a process for preparing the Alectinib or a pharmaceutically acceptable salt thereof using lesser reaction steps and also eliminating expensive and time- consuming column chromatography. The invention also relates to novel polymorphic forms of Alectinib and Alectinib hydrochloride.

  本发明涉及一种制备阿雷替尼或其药用盐的方法，该方法使用更少的反应步骤，并消除昂贵且耗时的柱层析过程。该发明还涉及阿雷替尼和阿雷替尼盐的新型多晶形态。
• SYNTHESIS OF INTERMEDIATES IN THE PREPARATION OF ALK INHIBITOR
  申请人：XU YONG

  公开号：US20160257667A1

  公开（公告）日：2016-09-08

  The present disclosure provides a method for preparing a compound of formula XVII, comprising: (1) contacting a compound of formula XIV with a compound of formula 3 to obtain a compound of formula 2; and (2) contacting the compound of formula 2 with a compound of formula 4 to obtain a compound of formula XVII. The method is low toxicity, cheap, easy to get, environmentally and friendly, and is economical and industrially applicable.

  本公开提供了一种制备化合物XVII的方法，包括：(1)将化合物XIV与化合物3接触以获得化合物2；(2)将化合物2与化合物4接触以获得化合物XVII。该方法毒性低、成本便宜、易获取、环保友好、经济实用，可在工业上应用。