trans-4-[9-ethyl-6-(3-nitro-phenylamino)-9H-purin-2-yl-amino]cyclohexanol | 289480-22-4

• 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: trans-4-[9-ethyl-6-(3-nitro-phenylamino)-9H-purin-2-yl-amino]cyclohexanol
• CAS: 289480-22-4
• 化学式: C₁₉H₂₃N₇O₃
• 分子量: 397.437
• InChiKey: LKALYIOCUAEKHT-NNUKFRKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.21
• 重原子数：
  29.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  131.03
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  trans-4-[9-ethyl-6-(3-nitro-phenylamino)-9H-purin-2-yl-amino]cyclohexanol 生成 4-[6-(3-amino-phenylamino)-9-isopropyl-9H-purin-2-ylamino]-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：

  2,6-二氯嘌呤 在 potassium carbonate 作用下， 以 戊醇 、 二乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 trans-4-[9-ethyl-6-(3-nitro-phenylamino)-9H-purin-2-yl-amino]cyclohexanol
  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：US06767906B2

  公开（公告）日：2004-07-27

  This application discloses 2-amino-6-anilino-purine derivatives of the formula I in which q is 1-5, and R1 is &agr;) —S(═O)k—NR6R7, in which  k is 1 or 2,  wherein under the proviso that R6 and R7 cannot be simultaneously hydrogen &agr;1) R6, R7 can be identical or different from one another and represent an aliphatic, carbocyclic, heterocyclic, carbocyclic-aliphatic or heterocyclic-aliphatic radical; hydrogen or lower aliphatic acyl; or &agr;2) R6 and R7 together are an alkylene or alkenylene radical having from 3 up to and including 9 C atoms, in which 1-3 C atoms can be replaced by oxygen, sulfur or nitrogen, &bgr;) N-(aryl lower alkyl)carbamoyl, or &ggr;) a radical of the formula —NH—S(═O)i—R8, in which  i is 1 or 2,  R8 is an aliphatic, carbocyclic or heterocyclic radical; or &dgr;) a radical of the formula —NH—C(═O)—R9,  and the other variable substituents are as defined herein. The inventive 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.

  本申请公开了式I的2-氨基-6-苯胺基嘌呤衍生物，其中q为1-5，R1为&agr;) -S（═O）k-NR6R7，其中k为1或2，在R6和R7不能同时为氢的前提下&agr;1）R6，R7可以相同或不同，表示脂肪族，环烷，杂环，环烷基-脂肪族或杂环-脂肪族基；氢或较低的脂肪酰基；或&agr;2）R6和R7在一起是具有3到9个C原子的烷基或烯基基团，其中1-3个C原子可以被氧，硫或氮取代，&bgr;) N-（芳基较低烷基）氨基甲酰基，或&ggr;) 公式-NH-S（═O）i-R8的基团，在其中i为1或2，R8为脂肪族，环烷或杂环基团；或&dgr;) 公式-NH-C（═O）-R9的基团，其它可变取代基的定义如本文所述。这些创新化合物抑制p34cdc2 / cyclin Bcdc13激酶和蛋白酪氨酸激酶pp60c-src，并可用于治疗增生性疾病，例如肿瘤疾病和对蛋白酪氨酸激酶pp60c-src活性抑制有反应的疾病，特别是骨质疏松症。
• 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