4-(2,6-dichloro-9H-purin-9-yl)benzamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(2,6-dichloro-9H-purin-9-yl)benzamide
• 英文别名: 4-(2,6-Dichloropurin-9-yl)benzamide；4-(2,6-dichloropurin-9-yl)benzamide
• 化学式: C₁₂H₇Cl₂N₅O
• 分子量: 308.126
• InChiKey: UFEKMILKFUVPPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  86.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2,6-dichloro-9H-purin-9-yl)benzamide 在 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-2-((9-(4-carbamoylphenyl)-2-chloro-9H-purin-6-yl)amino)propanoic acid
  参考文献：
  名称：

  Targeting different binding sites in the CFTR structures allows to synergistically potentiate channel activity

  摘要：

  Recent evidence shows that combination of correctors and potentiators, such as the drug ivacaftor (VX-770), can significantly restore the functional expression of mutated Cystic Fibrosis Transmembrane conductance Regulator (CFTR), an anion channel which is mutated in cystic fibrosis (CF). The success of these combinatorial therapies highlights the necessity of identifying a broad panel of specific binding mode modulators, occupying several distinct binding sites at structural level. Here, we identified two small molecules, SBC040 and SBC219, which are two efficient cAMP-independent potentiators, acting at low concentration of forskolin with EC50 close to 1 mu M and in a synergic way with the drug VX-770 on several CFTR mutants of classes II and III. Molecular dynamics simulations suggested potential SBC binding sites at the vicinity of ATP-binding sites, distinct from those currently proposed for VX-770, outlining SBC molecules as members of a new family of potentiators. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112116
• 作为产物：
  描述：

  2-amino-5-{[(dimethylamino)methylene]amino}-4,6-dichloropyrimidine 在 亚硝酸特丁酯 、 苄基三乙基氯化铵 、 对甲苯磺酸 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 73.5h， 生成 4-(2,6-dichloro-9H-purin-9-yl)benzamide
  参考文献：
  名称：

  一锅合成高功能嘌呤

  摘要：

  使用适合Vilsmeier型试剂的Traube合成，通过一锅简单，无金属的可扩展方法，可以高产量合成高取代的嘌呤。由5-氨基-4-氯嘧啶，制备新的9-芳基取代的氯嘌呤和用于肽核酸合成的中间体。还报道了允许从5-ami基-6-氨基嘧啶快速合成核糖核苷和7-苄基嘌呤的各种方法，以说明这种多功能工具箱的巨大潜力。该途径在核酸领域中对于直接和快速地获得各种新的8-烷基嘌呤核苷似乎是特别令人感兴趣的。

  DOI：

  10.1021/acs.orglett.7b03209

文献信息

• [EN] METHOD FOR SYNTHESIZING DIVERSELY SUBSTITUTED PURINES<br/>[FR] PROCÉDÉ DE SYNTHÈSE DE PURINES À SUBSTITUTIONS DIVERSES
  申请人：UNIV GRENOBLE ALPES

  公开号：WO2018203099A1

  公开（公告）日：2018-11-08

  The present invention relates to a method for synthesizing diversely substituted purines starting from a pyrimidine. Formula (I). The method comprises the formation of an amidine group on the pyrimidine by implementing a Vilsmeier type reagent, the functionalization of the pyrimidine with an amine and the cyclization to form the purine nucleus. Optional steps can also be performed in order to further functionalize the molecule. The invention also relates to new purines and new intermediate product.

  本发明涉及一种从嘧啶开始合成多样取代嘌呤的方法。公式（I）。该方法包括通过实施Vilsmeier型试剂在嘧啶上形成酰胺基团，用胺对嘧啶进行官能化，并进行环化以形成嘌呤核。还可以执行可选步骤以进一步官能化分子。该发明还涉及新的嘌呤和新的中间产物。
• Compounds for treating cystic fibrosis
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)

  公开号：US10414768B2

  公开（公告）日：2019-09-17

  The present invention relates to compounds of Formula (I) or pharmaceutically acceptable enantiomers, salts, solvates or prodrugs thereof. The invention further relates to the use of the compounds of Formula (I) for the treatment of cystic fibrosis. The invention also relates to a process for manufacturing compounds of Formula (I).

  本发明涉及式（I）化合物或其药学上可接受的对映体、盐、溶液剂或原药。本发明还涉及式（I）化合物用于治疗囊性纤维化的用途。本发明还涉及一种制造式（I）化合物的工艺。
• [EN] COMPOUNDS FOR TREATING CYSTIC FIBROSIS<br/>[FR] COMPOSÉS POUR LE TRAITEMENT DE LA FIBROSE KYSTIQUE
  申请人：CENTRE NAT DE LA RECH SCIENT (CNRS)

  公开号：WO2016087665A3

  公开（公告）日：2016-09-09
• COMPOUNDS FOR TREATING CYSTIC FIBROSIS
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)

  公开号：US20170362239A1

  公开（公告）日：2017-12-21

  The present invention relates to compounds of Formula (I) or pharmaceutically acceptable enantiomers, salts, solvates or prodrugs thereof. The invention further relates to the use of the compounds of Formula (I) for the treatment of cystic fibrosis. The invention also relates to a process for manufacturing compounds of Formula (I).
• METHOD FOR SYNTHESIZING DIVERSELY SUBSTITUTED PURINES
  申请人：UNIVERSITE GRENOBLE ALPES

  公开号：US20210163484A1

  公开（公告）日：2021-06-03

  The present invention relates to a method for synthesizing diversely substituted purines starting from a pyrimidine. Formula (I). The method comprises the formation of an amidine group on the pyrimidine by implementing a Vilsmeier type reagent, the functionalization of the pyrimidine with an amine and the cyclization to form the purine nucleus. Optional steps can also be performed in order to further functionalize the molecule. The invention also relates to new purines and new intermediate product.