(S)-2-(5-fluoro-2-(hydroxymethyl)-3-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one | 1433989-25-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (S)-2-(5-fluoro-2-(hydroxymethyl)-3-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one
• 英文别名: 2-[5-fluoro-2-(hydroxymethyl)-3-[1-methyl-5-[[5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]phenyl]-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1-one
• CAS: 1433989-25-3
• 化学式: C₃₇H₄₂FN₇O₄
• 分子量: 667.783
• InChiKey: VMQMTEKWNWDCEK-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  49
• 可旋转键数：
  7
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4,5,6,7-四氢吲哚 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium phosphate monohydrate 、 palladium 10% on activated carbon 、 水 、 氢气 、 sodium ethanolate 、 potassium acetate 、 sodium acetate 、 sodium hydride 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 乙酸乙酯 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 异丙醇 、 乙腈 、 mineral oil 为溶剂， 20.0~110.0 ℃ 、344.75 kPa 条件下， 反应 47.5h， 生成 (S)-2-(5-fluoro-2-(hydroxymethyl)-3-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one
  参考文献：
  名称：

  ALKYLATED PIPERAZINE COMPOUNDS

  摘要：

  提供了公式I的烷基化哌嗪化合物，包括其立体异构体、互变异构体和药学上可接受的盐，用于抑制Btk激酶，并用于治疗由Btk激酶介导的炎症等免疫紊乱。公开了使用公式I化合物进行哺乳动物细胞中的体外、体内和体内诊断以及治疗这类疾病或相关病理条件的方法。

  公开号：

  US20130116245A1

文献信息

• Alkylated piperazine compounds
  申请人：Genentech, Inc.

  公开号：US08946213B2

  公开（公告）日：2015-02-03

  Alkylated piperazine compounds of Formula I are provided, including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating cancer mediated by Btk kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of cancer in mammalian cells, or associated pathological conditions, are disclosed.

  提供了式I的烷基化哌嗪化合物，包括立体异构体、互变异构体和其药学上可接受的盐，用于抑制Btk激酶并治疗由Btk激酶介导的癌症。公开了使用式I化合物进行哺乳动物细胞中癌症的体外、原位和体内诊断和治疗，或相关病理条件的方法。
• ALKYLATED PIPERAZINE COMPOUNDS AS INHIBITORS OF BTK ACTIVITY
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2773639B1

  公开（公告）日：2017-04-26
• EP3125920B1
  申请人：——

  公开号：EP3125920B1

  公开（公告）日：2020-12-23
• USE OF DIANHYDROGALACTITOL AND ANALOGS OR DERIVATIVES THEREOF IN COMBINATION WITH PLATINUM-CONTAINING ANTINEOPLASTIC AGENTS TO TREAT NON-SMALL-CELL CARCINOMA OF THE LUNG AND BRAIN METASTASES
  申请人：Del Mar Pharmaceuticals

  公开号：US20160008316A1

  公开（公告）日：2016-01-14

  The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of non-small-cell lung carcinoma (NSCLC) and ovarian cancer, as well as other types of malignancy, including brain metastases of NSCLC. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N 7 methylation. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide, cisplatin, and tyrosine kinase inhibitors; the drug acts independently of the MGMT repair mechanism. Dianhydrogalactitol can be used together with other anti-neoplastic agents and can possess additive or super-additive effects.
• USE OF DIANHYDROGALACTITOL AND ANALOGS OR DERIVATIVES THEREOF IN COMBINATION WITH PLATINUM-CONTAINING ANTINEOPLASTIC AGENTS TO TREAT NON-SMALL-CELL CARCINOMA OF THE LUNG AND BRAIN METASTASES
  申请人：BACHA Jeffrey

  公开号：US20180140571A1

  公开（公告）日：2018-05-24

  The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of non-small-cell lung carcinoma (NSCLC) and ovarian cancer, as well as other types of malignancy, including brain metastases of NSCLC. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N 7 methylation. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide, cisplatin, and tyrosine kinase inhibitors; the drug acts independently of the MGMT repair mechanism. Dianhydrogalactitol can be used together with other anti-neoplastic agents and can possess additive or super-additive effects.