N-(6-chloro-9-trityl-9H-purin-2-yl)-2,2,2-trifluoroacetamide | 1236151-84-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N-(6-chloro-9-trityl-9H-purin-2-yl)-2,2,2-trifluoroacetamide
• 英文别名: N-(6-Chloro-9-trityl-9H-purine-2-yl)-2,2,2-trifluoroacetamide；N-(6-chloro-9-tritylpurin-2-yl)-2,2,2-trifluoroacetamide
• CAS: 1236151-84-0
• 化学式: C₂₆H₁₇ClF₃N₅O
• 分子量: 507.902
• InChiKey: CJVMLRROGAKUOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  72.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  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 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 87.0h， 生成 N6-[(4-nitrophenyl)methyl]-N2-[[3-(trifluoromethyl)phenyl]methyl]-9-trityl-purine-2,6-diamine
  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
• 作为产物：
  描述：

  三苯基氯甲烷 在 吡啶 、 sodium hydride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 N-(6-chloro-9-trityl-9H-purin-2-yl)-2,2,2-trifluoroacetamide
  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

• Concise access to N9-mono-, N2-mono- and N2,N9-di-substituted guanines via efficient Mitsunobu reactions
  作者：Steven Fletcher、Vijay M. Shahani、Alan J. Lough、Patrick T. Gunning

  DOI：10.1016/j.tet.2010.03.118

  日期：2010.6

  Guanine poses several problems to the synthetic chemist owing to its polyfunctional nature and poor solubility. Over the past few decades, synthetic guanines have found applications as anti-cancer and anti-viral agents. Coupled with the ever-growing interest in designer PNAs and G-quartets, simple and efficient synthetic routes to novel guanines would be of significant benefit. We herein report that, upon simple protection and/or activation step(s), the guanine precursor 2-amino-6-chloropurine is rendered an excellent substrate for Mitsunobu chemistry, furnishing, after subsequent hydrolytic dechlorination and appropriate deprotection step(s), the desired N9-mono-, N2-mono- or N2,N9-di-substituted guanines in excellent yields (>= 80%). Importantly, we demonstrate that N9-functionalization proceeds with very good N9/N7 regioselectivity and with complete inversion of stereochemistry. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis and characterization of novel isoform-selective IP6K1 inhibitors
  作者：Michael M. Wormald、Glen Ernst、Huijun Wei、James C. Barrow

  DOI：10.1016/j.bmcl.2019.126628

  日期：2019.10

  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.