(2-chloro-9-ethyl-9H-purin-6-yl)-(3-nitro-phenyl)-amine | 289480-25-7

• 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-9-ethyl-9H-purin-6-yl)-(3-nitro-phenyl)-amine
• 英文别名: 2-chloro-9-ethyl-N-(3-nitrophenyl)purin-6-amine
• CAS: 289480-25-7
• 化学式: C₁₃H₁₁ClN₆O₂
• 分子量: 318.722
• InChiKey: KXGIINGOPBHASV-UHFFFAOYSA-N

物化性质

• 沸点：
  469.8±55.0 °C(Predicted)
• 密度：
  1.59±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2-chloro-9-ethyl-9H-purin-6-yl)-(3-nitro-phenyl)-amine 以35%的产率得到trans-4-[9-ethyl-6-(3-nitro-phenylamino)-9H-purin-2-yl-amino]cyclohexanol
  参考文献：
  名称：

  2-Amino-6-anilino-purines and their use as medicaments

  摘要：

  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。

  公开号：

  US20020016329A1
• 作为产物：
  描述：

  间硝基苯胺 在 potassium carbonate 作用下， 以 戊醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (2-chloro-9-ethyl-9H-purin-6-yl)-(3-nitro-phenyl)-amine
  参考文献：
  名称：

  Potent and orally active purine-based fetal hemoglobin inducers for treating β-thalassemia and sickle cell disease

  摘要：

  Reactivation of fetal hemoglobin (HbF) expression by therapeutic agents has been suggested as an alternative treatment to modulate anemia and the related symptoms of severe β-thalassemia and sickle cell disease (SCD). Hydroxyurea (HU) is the first US FDA-approved HbF inducer for treating SCD. However, approximately 25% of the patients with SCD do not respond to HU. A previous study identified TN1 (1) as a small-molecule HbF inducer. However, this study found that the poor potency and oral bioavailability of compound 1 limits the development of this inducer for clinical use. To develop drug-like compounds, further structure-activity relationship studies on the purine-based structure of 1 were conducted. Herein, we report our discovery of a more potent inducer, compound 13a, that can efficiently induce γ-globin gene expression at non-cytotoxic concentrations. The molecular mechanism of 13a, for the regulation HbF expression, was also investigated. In addition, we demonstrated that oral administration of 13a can ameliorate anemia and the related symptoms in SCD mice. The results of this study suggest that 13a can be further developed as a novel agent for treating hemoglobinopathies, such as β-thalassemia and SCD.

  DOI：

  10.1016/j.ejmech.2020.112938

文献信息

• 2-AMINO-6-ANILINO-PURINES AND THEIR USE AS MEDICAMENTS
  申请人：Novartis AG

  公开号：EP1153024B1

  公开（公告）日：2004-04-28
• US6767906B2
  申请人：——

  公开号：US6767906B2

  公开（公告）日：2004-07-27
• [EN] 2-AMINO-6-ANILINO-PURINES AND THEIR USE AS MEDICAMENTS<br/>[FR] 2-AMINO-6-ANILINO-PURINES ET LEUR UTILISATION COMME MEDICAMENTS
  申请人：NOVARTIS AG

  公开号：WO2000049018A1

  公开（公告）日：2000-08-24

  2-Amino-6-anilino-purine derivatives of formula (I) in which R1 is -S(O)k-NR6R7 or-N(aryl lower alkyl) carbamoyl or -NH-S(O)i-R8 or -NH-C(O)-R9; 9 is 1-5; These compounds inhibit p34cdc2/cyclin Bcdc13 kinase and protein tyrosine kinase pp60c-src and can be used for treatment of hyperproliferative diseases, for example tumour diseases, and diseases which respond to inhibition of the activity of protein tyrosine kinase pp60c-src, in particular osteoporosis.
• 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。
• Potent and orally active purine-based fetal hemoglobin inducers for treating β-thalassemia and sickle cell disease
  作者：Zheng-Sheng Lai、Teng-Kuang Yeh、Yu-Chi Chou、Tsu Hsu、Cheng-Tai Lu、Fang-Chun Kung、Ming-Yen Hsieh、Chun-Hung Lin、Chiung-Tong Chen、Che-Kun James Shen、Weir-Torn Jiaang

  DOI：10.1016/j.ejmech.2020.112938

  日期：2021.1

  Reactivation of fetal hemoglobin (HbF) expression by therapeutic agents has been suggested as an alternative treatment to modulate anemia and the related symptoms of severe β-thalassemia and sickle cell disease (SCD). Hydroxyurea (HU) is the first US FDA-approved HbF inducer for treating SCD. However, approximately 25% of the patients with SCD do not respond to HU. A previous study identified TN1 (1) as a small-molecule HbF inducer. However, this study found that the poor potency and oral bioavailability of compound 1 limits the development of this inducer for clinical use. To develop drug-like compounds, further structure-activity relationship studies on the purine-based structure of 1 were conducted. Herein, we report our discovery of a more potent inducer, compound 13a, that can efficiently induce γ-globin gene expression at non-cytotoxic concentrations. The molecular mechanism of 13a, for the regulation HbF expression, was also investigated. In addition, we demonstrated that oral administration of 13a can ameliorate anemia and the related symptoms in SCD mice. The results of this study suggest that 13a can be further developed as a novel agent for treating hemoglobinopathies, such as β-thalassemia and SCD.