6,6-Dimethyl-11-oxo-8-(1,2,3,6-tetrahydro-pyridin-4-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile | 1256577-84-0

• 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
• 英文名称: 6,6-Dimethyl-11-oxo-8-(1,2,3,6-tetrahydro-pyridin-4-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile
• 英文别名: 6,6-dimethyl-11-oxo-8-(1,2,3,6-tetrahydropyridin-4-yl)-5H-benzo[b]carbazole-3-carbonitrile
• CAS: 1256577-84-0
• 化学式: C₂₄H₂₁N₃O
• 分子量: 367.45
• InChiKey: HNEFKQIXMRCGAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  28
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  68.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6,6-Dimethyl-11-oxo-8-(1,2,3,6-tetrahydro-pyridin-4-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 在 N-羟基-7-氮杂苯并三氮唑 、 palladium 10% on activated carbon 、 氢气 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 6,6-dimethyl-8-(1-(morpholine-3-carbonyl)piperidin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile
  参考文献：
  名称：

  Novel tetracyclic benzo[b]carbazolones as highly potent and orally bioavailable ALK inhibitors: Design, synthesis, and structure—activity relationship study

  摘要：

  Four series of tetracyclic benzo[b]carbazolone compounds possessing more rotatable bonds and higher molecular flexibility were designed by either inserting a linker within the C8-side chain or by opening the middle ketone ring on the basis of compound 5 (Alectinib, CH5424802). Compound 15b was identified showing nearly identical high potency against both wild-type and the gatekeeper mutant ALK kinase (3.4 vs 3.9 nM). This compound has favorable PK profile with an oral bioavailability of 67.1% in rats. Moreover, compound 15b showed significant growth inhibition against ALK driven cancer cells and KARPAS-299 xenograft model. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.005
• 作为产物：
  描述：

  N-Boc-1,2,5,6-四氢吡啶-4-硼酸频哪醇酯 在 四(三苯基膦)钯 、 sodium carbonate 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 生成 6,6-Dimethyl-11-oxo-8-(1,2,3,6-tetrahydro-pyridin-4-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile
  参考文献：
  名称：

  Novel tetracyclic benzo[b]carbazolones as highly potent and orally bioavailable ALK inhibitors: Design, synthesis, and structure—activity relationship study

  摘要：

  Four series of tetracyclic benzo[b]carbazolone compounds possessing more rotatable bonds and higher molecular flexibility were designed by either inserting a linker within the C8-side chain or by opening the middle ketone ring on the basis of compound 5 (Alectinib, CH5424802). Compound 15b was identified showing nearly identical high potency against both wild-type and the gatekeeper mutant ALK kinase (3.4 vs 3.9 nM). This compound has favorable PK profile with an oral bioavailability of 67.1% in rats. Moreover, compound 15b showed significant growth inhibition against ALK driven cancer cells and KARPAS-299 xenograft model. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.005

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）。
• TETRACYCLIC COMPOUNDS
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP2975024A1

  公开（公告）日：2016-01-20

  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).

  下式（I）所代表的化合物或其盐或溶液，可作为 ALK 抑制剂，用于预防或治疗伴随 ALK 异常的疾病，例如癌症、癌症转移、抑郁症或认知功能障碍： (式中所含符号的含义与说明书中给出的相同）。
• US9126931B2
  申请人：——

  公开号：US9126931B2

  公开（公告）日：2015-09-08
• US9440922B2
  申请人：——

  公开号：US9440922B2

  公开（公告）日：2016-09-13
• Novel tetracyclic benzo[b]carbazolones as highly potent and orally bioavailable ALK inhibitors: Design, synthesis, and structure—activity relationship study
  作者：Xiaolong Jiang、Ji Zhou、Jing Ai、Zilan Song、Xia Peng、Li Xing、Yong Xi、Junfeng Guo、Qizheng Yao、Jian Ding、Meiyu Geng、Ao Zhang

  DOI：10.1016/j.ejmech.2015.10.005

  日期：2015.11

  Four series of tetracyclic benzo[b]carbazolone compounds possessing more rotatable bonds and higher molecular flexibility were designed by either inserting a linker within the C8-side chain or by opening the middle ketone ring on the basis of compound 5 (Alectinib, CH5424802). Compound 15b was identified showing nearly identical high potency against both wild-type and the gatekeeper mutant ALK kinase (3.4 vs 3.9 nM). This compound has favorable PK profile with an oral bioavailability of 67.1% in rats. Moreover, compound 15b showed significant growth inhibition against ALK driven cancer cells and KARPAS-299 xenograft model. (C) 2015 Elsevier Masson SAS. All rights reserved.