2-chloro-N-phenyl-9H-purin-6-amine | 185408-97-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2-chloro-N-phenyl-9H-purin-6-amine
• 英文别名: 2-chloro-N-phenyl-7H-purin-6-amine
• CAS: 185408-97-3
• 化学式: C₁₁H₈ClN₅
• 分子量: 245.671
• InChiKey: HKFOFMISVJXDFK-UHFFFAOYSA-N

物化性质

• 熔点：
  298 °C(Solv: water (7732-18-5))
• 沸点：
  371.9±52.0 °C(Predicted)
• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 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：
  66.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-N-phenyl-9H-purin-6-amine 在 水 、 potassium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 caesium carbonate 、 三乙胺 、 potassium iodide 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 乙腈 、 丁酮 为溶剂， 反应 1.34h， 生成 (E)-N-(2-aminophenyl)-3-(4-((2-((9-cyclopentyl-6-(phenylamino)-9H-purin-2-yl)amino)ethoxy)methyl)phenyl)acrylamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel histone deacetylase1/2 (HDAC1/2) and cyclin-dependent Kinase2 (CDK2) dual inhibitors against malignant cancer

  摘要：

  In the current study, we have designed and synthesized a series of novel histone deacetylase1/2 (HDAC1/2) and cyclin-dependent kinase2 (CDK2) dual inhibitors by integrating purine-based pharmacophore into the recognition cap group of CS055. The representative compound 14d with excellent anti-proliferative activities towards five solid cancer cells, showed potent inhibitory activities against HDAC1, HDAC2 and CDK2 with IC50 values of 70.7 nM, 23.1 nM and 0.80 mu M, respectively. Besides, compound 14d could effectively block the cell cycle in the G2/M phase and induce apoptosis, which might be related to increasing intracellular ROS levels. Importantly, compound 14d exhibited desirable pharmacokinetic (PK) properties with the intraperitoneal bioavailability of 50.8% in ICR mice, and potent in vivo antitumor activity in the HCT116 xenograft model. Therefore, compound 14d could be considered as a promising lead compound for the development of multitargeting anticancer agents. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112322
• 作为产物：
  描述：

  2-acetamido-9-acetyl-6-chloropurine 在 盐酸 、 水 、 copper(l) chloride 、 sodium hydroxide 、 sodium nitrite 作用下， 以 水 、 正丁醇 为溶剂， 生成 2-chloro-N-phenyl-9H-purin-6-amine
  参考文献：
  名称：

  Microwave assisted synthesis of 2,6-substituted aromatic-aminopurine derivatives

  摘要：

  AbstractA series of novel 2, 6‐diaromatic‐aminopurines (6a–6t) have been synthesized from guanine and characterized fully. The effects of different catalysts on the N‐alkylation of 2‐position of purine ring were discussed. J. Heterocyclic Chem., (2011).

  DOI：

  10.1002/jhet.629

文献信息

• Novel purine derivatives, preparation method and use as medicines
  申请人：Aventis Pharma S.A.

  公开号：US20040063732A1

  公开（公告）日：2004-04-01

  The use of purine derivatives of formula (I): 1 as cdk kinase inhibitors for the prevention and treatment of fungal infections. Also disclosed are novel methods and intermediates for the production of compounds of formula I, as well as pharmaceutical compositions containing said compounds.

  将式(I)的嘌呤衍生物用作CDK激酶抑制剂，用于预防和治疗真菌感染。还公开了用于制备式(I)化合物的新方法和中间体，以及含有该化合物的药物组合物。
• 2-Amino-6-anilino-purines and their use as medicaments
  申请人：——

  公开号：US20020016329A1

  公开（公告）日：2002-02-07

  2-Amino-6-anilino-purine derivatives of the formula I 1 in which the symbols are as defined in claim 1, are described. These compounds inhibit p34 cdc2 /cyclin B cdc13 kinase and protein tyrosine kinase pp60 c-src and can be used for treatment of hyperproliferative diseases, for example tumor diseases, and diseases which respond to inhibition of the activity of protein tyrosine kinase pp60 c-src , in particular osteoporosis.

  公式I中定义的符号如权利要求书1中所定义的那样，描述了1的2-氨基-6-苯胺基嘌呤衍生物。这些化合物抑制p34 cdc2/cyclin B cdc13激酶和蛋白酪氨酸激酶pp60 c-src，并可用于治疗过度增殖性疾病，例如肿瘤疾病，以及对蛋白酪氨酸激酶pp60 c-src活性抑制有反应的疾病，特别是骨质疏松症。
• Enantioselective and Regiodivergent Addition of Purines to Terminal Allenes: Synthesis of Abacavir
  作者：Niels Thieme、Bernhard Breit

  DOI：10.1002/anie.201610876

  日期：2017.2

  The rhodium‐catalyzed atom‐economic asymmetric N‐selective intermolecular addition of purine derivatives to terminal allenes is reported. Branched allylic purines were obtained in high yields, regioselectivity and outstanding enantioselectivity utilizing a Rh/Josiphos catalyst. Conversely, linear selective allylation of purines could be realized in good to excellent regio‐ and E/Z‐selectivity with

  据报道，铑催化的原子经济不对称的N选择性分子间嘌呤衍生物加成到末端亚丙基上。利用Rh / Josiphos催化剂以高收率，区域选择性和突出的对映选择性获得支链的烯丙基嘌呤。相反，使用Pd / dppf催化剂体系可以实现嘌呤的线性选择性烯丙基化，具有良好的区域选择性和E / Z选择性。此外，新方法被应用于碳环核苷阿巴卡韦的直接不对称合成。
• Method for treating disease or condition susceptible to amelioration by AMPK activators and compounds of formula which are useful to activate AMP-activated protein kinase (AMPK)
  申请人：CHEN Han-Min

  公开号：US20140303112A1

  公开（公告）日：2014-10-09

  The present invention relates to a method for treating disease or condition susceptible to amelioration by AMPK activators and compounds of formula which are useful to activate AMP-activated protein kinase (AMPK) and the use of the compounds in the prevention or treatment of disease, including pre-diabetes, type 2 diabetes, syndrome X, metabolic syndrome and obesity.

  本发明涉及一种治疗疾病或病情的方法，该疾病或病情容易通过AMPK激活剂和公式化合物得到改善，这些化合物有助于激活AMP激活蛋白激酶（AMPK），并将这些化合物用于预防或治疗疾病，包括糖尿病前期、2型糖尿病、X综合症、代谢综合征和肥胖症。
• Syntheses and Biological Evaluation of Novel Hydroxamic Acid Derivatives Containing Purine Moiety as Histone Deacetylase Inhibitors
  作者：Zhaoxing Xu、Yongchao Yang、Xi Mai、Bin Liu、Yuanzhen Xiong、Lihuang Feng、Yijing Liao、Yu Zhang、Huanlu Wang、Leiting Ouyang、Shuhao Liu

  DOI：10.1248/cpb.c17-00997

  日期：——

  acetyl histone H3 in a dose-dependent manner, which is similar to the behavior of suberoylanilide hydroxamic acid (SAHA). Molecular docking study revealed that the conformation of 7m' in the active site of HDAC2 was similar to positive drug SAHA, which were oriented with the hydroxamic acid towards the catalytic center and formed metal binding with zinc ion.

  设计，合成和筛选了含有嘌呤支架的新型异羟肟酸酯作为组蛋白脱乙酰基酶（HDAC）抑制剂的生物学活性。其中一些表现出优异的acti-HDACs活性和抗增殖活性，最有希望的化合物是7m'。Western印迹分析表明，化合物7f'，7l'，7m'，7o'可以增加HCT116和K562细胞株中组蛋白H3的乙酰化水平，而7m'则以剂量依赖的方式增加乙酰基组蛋白H3的水平，这相似异戊酰苯胺异羟肟酸（SAHA）的行为。分子对接研究表明，HDAC2活性位点中的7m'构象与阳性药物SAHA相似，后者被异羟肟酸定向至催化中心，并与锌离子形成金属结合。