7-chloro-1-(difluoromethyl)-8-phenyl-[1,2,4]triazolo[4,3-a]-1,5-naphthyridine | 1199557-02-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 7-chloro-1-(difluoromethyl)-8-phenyl-[1,2,4]triazolo[4,3-a]-1,5-naphthyridine
• 英文别名: 7-Chloro-1-(difluoromethyl)-8-phenyl[1,2,4]triazolo[4,3-a]-1,5-naphthyridine；7-chloro-1-(difluoromethyl)-8-phenyl-[1,2,4]triazolo[4,3-a][1,5]naphthyridine
• CAS: 1199557-02-2
• 化学式: C₁₆H₉ClF₂N₄
• 分子量: 330.724
• InChiKey: MSRDNTLYGJNLEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  43.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-chloro-1-(difluoromethyl)-8-phenyl-[1,2,4]triazolo[4,3-a]-1,5-naphthyridine 、 2-{trans-3-hydroxy-3-methyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclobutyl}-1H-isoindole-1,3(2H)-dione 在 四(三苯基膦)钯 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 生成 2-(trans-1-{4-[1-(difluoromethyl)-8-phenyl-[1,2,4]triazolo[4,3-a]-1,5-naphthyridin-7-yl]phenyl}-3-hydroxy-3-methylcyclobutyl)-1H-isoindole-1,3(2H)-dione
  参考文献：
  名称：

  [EN] INHIBITORS OF AKT ACTIVITY
  [FR] INHIBITEURS DE L'ACTIVITÉ AKT

  摘要：

  该瞬时发明提供了取代的[1,2,4]三唑并[4,3-a]-1,5-萘啶化合物，可以抑制Akt活性。具体来说，所披露的化合物选择性地抑制Akt同工酶中的一个或两个，最好是Akt1。该发明还提供了包含这种抑制化合物的组合物以及通过向需要癌症治疗的患者施用该化合物来抑制Akt活性的方法。

  公开号：

  WO2009148887A1
• 作为产物：
  描述：

  3-氨基-2-溴-6-氯吡啶 在 1,3-二甲基-2-咪唑啉酮 、 甲基锂 、 sodium hexamethyldisilazane 、 caesium carbonate 、 N,N-二异丙基乙胺 、 肼 、 三氯氧磷 作用下， 以 四氢呋喃 、 二乙氧基甲烷 、 水 、 乙腈 为溶剂， -55.0~155.0 ℃ 、344.75 kPa 条件下， 反应 18.25h， 生成 7-chloro-1-(difluoromethyl)-8-phenyl-[1,2,4]triazolo[4,3-a]-1,5-naphthyridine
  参考文献：
  名称：

  Convergent, Kilogram Scale Synthesis of an Akt Kinase Inhibitor

  摘要：

  The development of a convergent, chromatography-free synthesis of an allosteric Akt kinase inhibitor is described. The route comprised 17 total steps and was used to produce kilogram quantities of the target molecule. A key early transformation, for which both batch and flow protocols were developed, was formylation of a dianion derived by deprotonation and subsequent lithium-halogen exchange from a 2-bromo-3-aminopyridine precursor. Improved reaction yield and practicality were achieved in the continuous processing mode. Further significant process developments included the safe execution of a high temperature and pressure hydrazine displacement, separation of substituted cyclobutane diastereomers by means of chemoselective ester hydrolysis, and a late-stage Suzuki fragment coupling under mild conditions.

  DOI：

  10.1021/op300031r

文献信息

• INHIBITORS OF AKT ACTIVITY
  申请人：Furuyama Hidetomo

  公开号：US20110082135A1

  公开（公告）日：2011-04-07

  The instant invention provides for substituted [1,2,4]triazolo[4,3-a]-1,5-naphthyridine compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms, preferably Akt1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity, especially Akt1 by administering the compound to a patient in need of treatment of cancer.

  本发明提供了替代[1,2,4]三唑并[4,3-a]-1,5-萘啉化合物，其抑制Akt活性。特别地，所披露的化合物选择性地抑制一个或两个Akt亚型，优选是Akt1。本发明还提供了包含此类抑制剂化合物的组合物以及通过向需要治疗癌症的患者施用该化合物来抑制Akt活性，特别是Akt1的方法。
• Inhibitors of AKT activity
  申请人：Furuyama Hidetomo

  公开号：US08536193B2

  公开（公告）日：2013-09-17

  The instant invention provides for substituted [1,2,4]triazolo[4,3-a]-1,5-naphthyridine compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms, preferably Akt1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity, especially Akt1 by administering the compound to a patient in need of treatment of cancer.

  本发明提供了替代[1,2,4]三唑并[4,3-a]-1,5-萘啉化合物，其抑制Akt活性。具体而言，所披露的化合物选择性地抑制一种或两种Akt亚型，优选是Akt1。本发明还提供了包含这种抑制化合物的组合物以及通过向需要癌症治疗的患者施用该化合物来抑制Akt活性，特别是Akt1的方法。
• US8536193B2
  申请人：——

  公开号：US8536193B2

  公开（公告）日：2013-09-17
• [EN] INHIBITORS OF AKT ACTIVITY<br/>[FR] INHIBITEURS DE L'ACTIVITÉ AKT
  申请人：MERCK & CO INC

  公开号：WO2009148887A1

  公开（公告）日：2009-12-10

  The instant invention provides for substituted [1,2,4]triazolo[4,3-a]-1,5-naphthyridine compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms, preferably Akt1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity, especially Akt1 by administering the compound to a patient in need of treatment of cancer.

  该瞬时发明提供了取代的[1,2,4]三唑并[4,3-a]-1,5-萘啶化合物，可以抑制Akt活性。具体来说，所披露的化合物选择性地抑制Akt同工酶中的一个或两个，最好是Akt1。该发明还提供了包含这种抑制化合物的组合物以及通过向需要癌症治疗的患者施用该化合物来抑制Akt活性的方法。
• Convergent, Kilogram Scale Synthesis of an Akt Kinase Inhibitor
  作者：Pintipa Grongsaard、Paul G. Bulger、Debra J. Wallace、Lushi Tan、Qinghao Chen、Sarah J. Dolman、Jason Nyrop、R. Scott Hoerrner、Mark Weisel、Juan Arredondo、Takahiro Itoh、Chengfu Xie、Xianghui Wen、Dalian Zhao、Daniel J. Muzzio、Ephraim M. Bassan、C. Scott Shultz

  DOI：10.1021/op300031r

  日期：2012.5.18

  The development of a convergent, chromatography-free synthesis of an allosteric Akt kinase inhibitor is described. The route comprised 17 total steps and was used to produce kilogram quantities of the target molecule. A key early transformation, for which both batch and flow protocols were developed, was formylation of a dianion derived by deprotonation and subsequent lithium-halogen exchange from a 2-bromo-3-aminopyridine precursor. Improved reaction yield and practicality were achieved in the continuous processing mode. Further significant process developments included the safe execution of a high temperature and pressure hydrazine displacement, separation of substituted cyclobutane diastereomers by means of chemoselective ester hydrolysis, and a late-stage Suzuki fragment coupling under mild conditions.