N6-[(4-硝基苯基)甲基]-N2-[[3-(三氟甲基)苯基]甲基]-9H-嘌呤-2,6-二胺 | 519178-28-0

• 物质功能分类: 生物化工 - 抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: N6-[(4-硝基苯基)甲基]-N2-[[3-(三氟甲基)苯基]甲基]-9H-嘌呤-2,6-二胺
• 英文名称: TNP
• 英文别名: N²-(m-trifluorobenzyl)-N⁶-(p-nitrobenzyl)purine；IP3K Inhibitor；6-N-[(4-nitrophenyl)methyl]-2-N-[[3-(trifluoromethyl)phenyl]methyl]-7H-purine-2,6-diamine
• CAS: 519178-28-0
• 化学式: C₂₀H₁₆F₃N₇O₂
• 分子量: 443.388
• InChiKey: DDSBPUYZPWNNGH-UHFFFAOYSA-N

物化性质

• 沸点：
  723.4±70.0 °C(Predicted)
• 密度：
  1.543±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：≥10mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  124
• 氢给体数：
  3
• 氢受体数：
  10

制备方法与用途

生物活性

TNP是IP6K1和IP3K的抑制剂，其对IP6K1和IP3K的IC50值分别为0.55 µM和10.2 μM。TNP与两个酶的ATP结合位点相结合。

靶点

IC50: 0.55 µM (IP6K1), 10.2 μM (IP3K).

反应信息

• 作为产物：
  描述：

  N-(6-chloro-9-trityl-9H-purin-2-yl)-2,2,2-trifluoroacetamide 在 甲醇 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 110.0h， 生成 N6-[(4-硝基苯基)甲基]-N2-[[3-(三氟甲基)苯基]甲基]-9H-嘌呤-2,6-二胺
  参考文献：
  名称：

  Synthesis and characterization of novel isoform-selective IP6K1 inhibitors

  摘要：

  Inositol hexakisphosphate kinases (IP6Ks) have been increasingly studied as therapeutically interesting enzymes. IP6K isoform specific knock-outs have been used to successfully explore inositol pyrophosphate physiology and related pathologies. A pan-IP6K inhibitor, N2-(m-trifluorobenzyl)-N6-(p-nitrobenzyl) purine (TNP), has been used to confirm phenotypes observed in genetic knock-out experiments; however, it suffers by having modest potency and poor solubility making it difficult to handle for in vitro applications in the absence of DMSO. Moreover, TNP's pan-IP6K inhibitory profile does not inform which IP6K isoform is responsible for which phenotypes. In this report we describe a series of purine-based isoform specific IP6K1 inhibitors. The lead compound was identified after multiple rounds of SAR and has been found to selectively inhibit IP6K1 over IP6K2 or IP6K3 using biochemical and biophysical approaches. It also boasts increased solubility and IP6K1 potency over TNP. These new compounds are useful tools for additional assay development and exploration of IP6K1 specific biology.

  DOI：

  10.1016/j.bmcl.2019.126628

文献信息

• PHARMACEUTICAL COMPOSITION FOR SUPPRESSING APPETITE, CONTAINING N2-(M-TRIFLUOROBENZYL), N6-(P-NITROBENZYL)PURINE (TNP) OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF AS ACTIVE INGREDIENT
  申请人：Korea Advanced Institute of Science and Technology

  公开号：EP3443963A1

  公开（公告）日：2019-02-20

  The present invention relates to a pharmaceutical composition containing TNP (N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine) or a pharmaceutically acceptable salt thereof as an active ingredient for suppressing appetite. Particularly, TNP or a pharmaceutically acceptable salt thereof can be effectively used as an active ingredient of a pharmaceutical composition or a nutraceutical food for suppressing appetite since it is confirmed that food intake is reduced and weight gain is inhibited in mice when the central nervous system of mice is treated with TNP.

  本发明涉及一种含有 TNP（N2-(间三氟苄基)，N6-(对硝基苄基)嘌呤）或其药学上可接受的盐作为抑制食欲的活性成分的药物组合物。特别是，TNP 或其药学上可接受的盐可以有效地用作抑制食欲的药物组合物或营养保健食品的活性成分，因为已证实用 TNP 处理小鼠的中枢神经系统时，小鼠的食物摄入量会减少，体重增加会受到抑制。
• METHOD FOR MODULATING AUTOPHAGY AND APPLICATIONS THEREOF
  申请人：Jawaharlal Nehru Centre For Advanced Scientific Research

  公开号：EP3386498A1

  公开（公告）日：2018-10-17
• METHODS FOR PROMOTING CELL REPROGRAMMING
  申请人：Rana Tariq M.

  公开号：US20130064799A1

  公开（公告）日：2013-03-14

  The present invention is based on the seminal discovery that several kinases play important roles in barrier pathways in somatic cell reprogramming. The present invention provides that modulating expression or activity of these kinases can significantly promote or enhance cell reprogramming efficiency. Key kinases are identified and key regulation networks involving such kinases are also identified that may be advantageously targeted to significantly increase reprogramming efficiency as well as direct differentiation of induced pluripotent stem (iPS) cells.
• Composition for Preventing and Treating Acetaminophen Inducing Hepatotoxicity Containing TNP(N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine) as an Effective Ingredient
  申请人：KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY

  公开号：US20160354378A1

  公开（公告）日：2016-12-08

  The present invention relates to a composition for the prevention and treatment of liver toxicity originated from acetaminophen comprising TNP (N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine) as an active ingredient. The present inventors confirmed that TNP known as a 5-inosito pyrophosphate inhibitor suppressed apoptosis caused by acetaminophen in human embryonic stem cell-derived liver cells, mouse liver cells, and human hepatoma cell lines, up-regulated glutathione converted in liver cells, and inhibited JNK phosphorylation that is a kind of response against stress increased by acetaminophen. The inventors further confirmed that TNP had the activity of protecting liver cells from the toxicity caused by acetaminophen in an animal model. Therefore, TNP can be efficiently used as an active ingredient for a composition for the prevention and treatment of liver toxicity caused by acetaminophen.
• TKI PERMEABILITY ENHANCERS
  申请人：City of Hope

  公开号：US20190083650A1

  公开（公告）日：2019-03-21

  Provided herein are, inter alia, methods useful for delivering nucleic acids and kinase inhibitors to a cell. The methods provided herein include the delivery of therapeutic nucleic acids to cancer cells by contacting a cancer cell with a kinase inhibitor and a therapeutic nucleic acid. The methods provided herein are therefore, inter alia, useful for the treatment of cancer.