6-chloro-3-((methylamino)methyl)-N-(3-(trifluoromethyl)phenyl)-1,5-naphthyridin-4-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-chloro-3-((methylamino)methyl)-N-(3-(trifluoromethyl)phenyl)-1,5-naphthyridin-4-amine
• 英文别名: 6-chloro-3-(methylaminomethyl)-N-[3-(trifluoromethyl)phenyl]-1,5-naphthyridin-4-amine
• 化学式: C₁₇H₁₄ClF₃N₄
• 分子量: 366.773
• InChiKey: BZKGFIRVARKYEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  49.8
• 氢给体数：
  2
• 氢受体数：
  7

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	6-chloro-4-((3-(trifluoromethyl)phenyl)amino)-1,5-naphthyridine-3-carbaldehyde	1416000-54-8	C16H9ClF3N3O	351.715
  ——	ethyl 6-chloro-4-((3-(trifluoromethyl)phenyl)amino)-1,5-naphthyridine-3-carboxylate	1416000-52-6	C18H13ClF3N3O2	395.768

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	9-chloro-3-methyl-1-(3-(trifluoromethyl)phenyl)-3,4-dihydropyrimido[5,4-c][1,5]naphthyridin-1(2H)-one	——	C18H12ClF3N4O	392.768
  ——	9-(2-aminopyrimidin-5-yl)-3-methyl-1-(3-(trifluoromethyl)phenyl)-3,4-dihydropyrimido[5,4-c][1,5]naphthyridin-1(2H)-one	——	C22H16F3N7O	451.411
  ——	9-(6-aminopyridin-3-yl)-3-methyl-1-(3-(trifluoromethyl)phenyl)-3,4-dihydropyrimido[5,4-c][1,5]naphthyridin-1(2H)-one	——	C23H17F3N6O	450.423
  ——	N-(5-(3-methyl-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimido[5,4-c][1,5]naphthyridin-9-yl)pyridin-2-yl)acetamide	——	C25H19F3N6O2	492.46
  ——	3-methyl-9-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1-(3-(trifluoromethyl)phenyl)-3,4-dihydropyrimido[5,4-c][1,5]naphthyridin-1(2H)-one	——	C25H17F3N6O	474.445

反应信息

• 作为反应物：
  描述：

  6-chloro-3-((methylamino)methyl)-N-(3-(trifluoromethyl)phenyl)-1,5-naphthyridin-4-amine 在 四(三苯基膦)钯 、 sodium carbonate 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 8.0h， 生成 9-(6-aminopyridin-3-yl)-3-methyl-1-(3-(trifluoromethyl)phenyl)-3,4-dihydropyrimido[5,4-c][1,5]naphthyridin-1(2H)-one
  参考文献：
  名称：

  THREE-RING PI3K AND/OR MTOR INHIBITOR

  摘要：

  本申请涉及一种由通式（I）表示的化合物，其药学上可接受的盐、酯、溶剂合物或立体异构体，该化合物的制备方法，含有该化合物的药物组合物，以及在制备用于治疗和/或预防增殖性疾病的药物中使用它们的用途，以及使用该化合物治疗和/或预防增殖性疾病的方法。通式中的R1、R2、R3、R4、R5、R6、X、A和B如规范中所定义。

  公开号：

  US20150166539A1
• 作为产物：
  描述：

  2-溴-5-硝基吡啶 在 盐酸 、 manganese(IV) oxide 、 sodium tetrahydroborate 、 铁粉 、 碳酸氢钠 、 potassium carbonate 、 三氯氧磷 作用下， 以 二苯醚 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基苯胺 、 叔丁醇 为溶剂， 反应 70.75h， 生成 6-chloro-3-((methylamino)methyl)-N-(3-(trifluoromethyl)phenyl)-1,5-naphthyridin-4-amine
  参考文献：
  名称：

  THREE-RING PI3K AND/OR MTOR INHIBITOR

  摘要：

  公开号：

  EP2781520B1

文献信息

• Three-ring PI3K and/or mTOR inhibitor
  申请人：XUANZHU PHARMA CO., LTD.

  公开号：US09284315B2

  公开（公告）日：2016-03-15

  The present application relates to a compound as represented by general formula (I), a pharmaceutically acceptable salt, ester, solvate or stereoisomer thereof, preparation method of the compounds, a pharmaceutical composition containing the compounds, uses thereof in the preparation of drugs for treating and/or preventing proliferative diseases, and a method using the compounds to treat and/or prevent proliferative diseases. R1, R2, R3, R4, R5, R6, X, A and B in the formula are as defined in the specification.

  本申请涉及一种由通式（I）表示的化合物，其药学上可接受的盐、酯、溶剂合物或立体异构体，该化合物的制备方法，含有该化合物的制药组合物，以及在制备用于治疗和/或预防增生性疾病的药物时使用该化合物的方法。式中的R1、R2、R3、R4、R5、R6、X、A和B在说明书中定义。
• US9284315B2
  申请人：——

  公开号：US9284315B2

  公开（公告）日：2016-03-15
• Developing a novel dual PI3K–mTOR inhibitor from the prodrug of a metabolite
  作者：Yan Zhou、Genyan Zhang、Feng Wang、Jin Wang、Yanwei Ding、Xinyu Li、Chongtie Shi、Jiakui Li、Chengkon Shih、Song You

  DOI：10.2147/ott.s142492

  日期：——

  This study presents a process of developing a novel PI3K-mTOR inhibitor through the prodrug of a metabolite. The lead compound (compound 1) was identified with similar efficacy as that of NVP-BEZ235 in a tumor xenograft model, but the exposure of compound 1 was much lower than that of NVP-BEZ235. After reanalysis of the blood sample, a major metabolite (compound 2) was identified. Compound 2 exerted similar in vitro activity as compound 1, which indicated that compound 2 was an active metabolite and that the in vivo efficacy in the animal model came from compound 2 instead of compound 1. However, compound 1 was metabolized into compound 2 predominantly in the liver microsomes of mouse, but not in the liver microsomes of rat, dog, or human. In order to translate the efficacy in the animal model into clinical development or predict the pharmacokinetic/pharmacodynamic parameters in the clinical study using a preclinical model, we developed the metabolite (compound 2) instead of compound 1. Due to the low bioavailability of compound 2, its prodrug (compound 3) was designed and synthesized to improve the solubility. The prodrug was quickly converted to compound 2 through both intravenous and oral administrations. Because the prodrug (compound 3) did not improve the oral exposure of compound 2, developing compound 3 as an intravenous drug was considered by our team, and the latest results will be reported in the future.
• THREE-RING PI3K AND/OR MTOR INHIBITOR
  申请人：Xuanzhu Pharma Co., Ltd.

  公开号：EP2781520B1

  公开（公告）日：2016-05-04