trans-3-amino-3-{4-[1-(difluoromethyl)-8-phenyl-[1,2,4]triazolo[4,3-a]-1,5-naphthyridin-7-yl]phenyl}-1-methylcyclobutanol | 1199556-40-5

• 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: trans-3-amino-3-{4-[1-(difluoromethyl)-8-phenyl-[1,2,4]triazolo[4,3-a]-1,5-naphthyridin-7-yl]phenyl}-1-methylcyclobutanol
• CAS: 1199556-40-5
• 化学式: C₂₇H₂₃F₂N₅O
• 分子量: 471.509
• InChiKey: MWUMSPLWAFDYMT-MCZWQBSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.25
• 重原子数：
  35.0
• 可旋转键数：
  4.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  89.33
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  6-hydrazinyl-3-phenyl-1,5-naphthyridin-2(1H)-one 在 四(三苯基膦)钯 二氟乙酸 、 sodium carbonate 、 一水合肼 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙醇 、 MDI 、 乙腈 为溶剂， 反应 4.0h， 生成 trans-3-amino-3-{4-[1-(difluoromethyl)-8-phenyl-[1,2,4]triazolo[4,3-a]-1,5-naphthyridin-7-yl]phenyl}-1-methylcyclobutanol
  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

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。
• US8536193B2
  申请人：——

  公开号：US8536193B2

  公开（公告）日：2013-09-17
• [EN] COMPOSITIONS AND METHODS TO IMPROVE THE THERAPEUTIC BENEFIT OF SUBOPTIMALLY ADMINISTERED CHEMICAL COMPOUNDS INCLUDING SUBSTITUTED NAPHTHALIMIDES SUCH AS AMONAFIDE FOR THE TREATMENT OF IMMUNOLOGICAL, METABOLIC, INFECTIOUS, AND BENIGN OR NEOPLASTIC HYPERPROLIFERATIVE DISEASE CONDITIONS<br/>[FR] COMPOSITIONS ET PROCÉDÉS PERMETTANT D'AMÉLIORER LE BÉNÉFICE THÉRAPEUTIQUE DES COMPOSÉS CHIMIQUES ADMINISTRÉS DE MANIÈRE SUBOPTIMALE COMPRENANT DES NAPHTALIMIDES SUBSTITUÉS TELS QUE L'AMONAFIDE POUR LE TRAITEMENT DES MALADIES IMMUNOLOGIQUES, MÉTABOLIQUES, INFECTIEUSES ET INFECTIEUSES OU HYPERPROLIFÉRATIVES ET NÉOPLASTIQUES.
  申请人：BROWN DENNIS M

  公开号：WO2014179528A2

  公开（公告）日：2014-11-06

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to naphthalimides such as amonafide or analogs, derivatives, or prodrugs thereof.
• [EN] USE OF DIANHYDROGALACTITOL OR DERIVATIVES OR ANALOGS THEREOF FOR TREATMENT OF PEDIATRIC CENTRAL NERVOUS SYSTEM MALIGNANCIES<br/>[FR] UTILISATION DE DIANHYDROGALACTITOL OU DES DÉRIVÉS OU ANALOGUES DE CELUI-CI POUR LE TRAITEMENT DE TUMEURS MALIGNES DU SYSTÈME NERVEUX CENTRAL PÉDIATRIQUE
  申请人：DELMAR PHARMACEUTICALS INC

  公开号：WO2017075052A1

  公开（公告）日：2017-05-04

  The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of malignancies of the central nervous system in pediatric patients, including glioblastoma multiforme (GBM) high grade glioma, and medulloblastoma. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N7 methylation and that can induce double-stranded breaks in DNA. 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 (e.g. cisplatin) and can possess additive or super-additive effects.
• [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。