2-氯-N-(3-氯苯基)-9-异丙基-9H-嘌呤-6-胺 | 190654-78-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 2-氯-N-(3-氯苯基)-9-异丙基-9H-嘌呤-6-胺
• 英文名称: 2-chloro-N-(3-chlorophenyl)-9-isopropyl- 9H-purin-6-amine
• 英文别名: 2-Chloro-N-(3-chlorophenyl)-9-isopropyl-9H-purin-6-amine；2-chloro-N-(3-chlorophenyl)-9-propan-2-ylpurin-6-amine
• CAS: 190654-78-5
• 化学式: C₁₄H₁₃Cl₂N₅
• 分子量: 322.197
• InChiKey: ZHIMHIHAHRYXJY-UHFFFAOYSA-N

物化性质

• 熔点：
  131.3-132.3 °C
• 沸点：
  460.7±55.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-氯-N-(3-氯苯基)-9-异丙基-9H-嘌呤-6-胺 在 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 173.0h， 生成 N²-((1R,2S)-2-aminocyclohexyl)-N⁶-(3-chlorophenyl)-9-isopropyl-9H-purine-2,6-diamine trifluoroacetate
  参考文献：
  名称：

  A triple exon-skipping luciferase reporter assay identifies a new CLK inhibitor pharmacophore

  摘要：

  The splicing of pre-mRNA is a critical process in normal cells and is deregulated in cancer. Compounds that modulate this process have recently been shown to target a specific vulnerability in tumors. We have developed a novel cell-based assay that specifically activates luciferase in cells exposed to SF3B1 targeted compounds, such as sudemycin D6. This assay was used to screen a combined collection of approved drugs and bioactive compounds. This screening approach identified several active hits, the most potent of which were CGP-74514A and aminopurvalanol A, both have been reported to be cyclin-dependent kinases (CDKs) inhibitors. We found that these compounds, and their analogs, show significant cdc2-like kinase (CLK) inhibition and clear structure-activity relationships (SAR) at CLKs. We prepared a set of analogs and were able to 'dial out' the CDK activity and simultaneously developed CLK inhibitors with low nanomolar activity. Thus, we have demonstrated the utility of our exon-skipping assay and identified new molecules that exhibit potency and selectivity for CLK, as well as some structurally related dual CLK/CDK inhibitors. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.12.056
• 作为产物：
  描述：

  2,6-二氯嘌呤 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 45.0h， 生成 2-氯-N-(3-氯苯基)-9-异丙基-9H-嘌呤-6-胺
  参考文献：
  名称：

  作为细胞周期蛋白依赖性激酶抑制剂的 C-2、C-8、N-9 取代的 6-(3-氯苯胺基)-嘌呤衍生物的合成和生物学特性。第二部分

  摘要：

  在这项研究中，合成了 C-2、C-8、N-9 取代的 6-(3-氯苯胺基)嘌呤衍生物，并评估了它们对细胞周期蛋白依赖性激酶 (CDK2, 4) 的抑制作用及其细胞毒性。研究了取代嘌呤的 C-2、C-8 和 N-9 位取代基的影响。在测试的化合物中，[6-(3-chloroanilino)-2-(2-hydroxymethyl-4-hydroxypyrrolidyl)-9-isopropylpurine] (4h) 是最有效的 CDK2 抑制剂，IC50 为 0.3μM，即双-与roscovitine相比，抑制活性成倍增加。构效关系研究的结果应该允许设计更有效和选择性的 CDK2 抑制剂，这可能为癌症或其他 CDK 依赖性疾病提供有效的治疗方法。

  DOI：

  10.1002/1521-4184(200112)334:11<345::aid-ardp345>3.0.co;2-1

文献信息

• Oxidative Amination of Cuprated Pyrimidine and Purine Derivatives
  作者：Nadège Boudet、Srinivas Reddy Dubbaka、Paul Knochel

  DOI：10.1021/ol800353s

  日期：2008.5.1

  Using regioselective cuprations (via magnesiations), various primary, secondary and tertiary aminated pyrimidine and purine derivatives were prepared by the oxidative coupling of lithium amidocuprates using chloranil. DNA and RNA units such as aminated uracil or thymine, and adenine, as well as a CDK inhibitor, purvalanol A, were all obtained under mild conditions and satisfactory yields.

  使用区域选择性的缩合（通过放大作用），通过使用氯苯胺对氨基cup酸锂进行氧化偶联，制备了各种伯胺，仲胺和叔胺基嘧啶和嘌呤衍生物。DNA和RNA单元（如胺化尿嘧啶或胸腺嘧啶，腺嘌呤）以及CDK抑制剂，嘌呤醇A，均在温和的条件下获得了令人满意的收率。
• [EN] DUAL CLK/CDK1 INHIBITORS FOR CANCER TREATMENT<br/>[FR] INHIBITEURS DOUBLES DE CLK/CDK1 DESTINÉS AU TRAITEMENT DU CANCER
  申请人：STANFORD RES INST INT

  公开号：WO2018064545A1

  公开（公告）日：2018-04-05

  This disclosure generally relates to dual CLK2/CDK1 inhibitors or more potent and specific CLK inhibitors to target CLK2 and CDKl kinases in the treatment of germ-line mutations of the spliceosome leading to the development of cancers and other human disease. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本公开一般涉及双重CLK2/CDK1抑制剂或更强效、更特异的CLK抑制剂，用于治疗导致癌症和其他人类疾病发展的剪接体的生殖细胞系突变。本摘要旨在作为在特定领域进行搜索的扫描工具，不打算限制本发明。
• [EN] PURINE DERIVATIVES AND PROCESSES FOR THEIR PREPARATION<br/>[FR] DERIVES PURINES ET PROCEDES DE PREPARATION ASSOCIES
  申请人：NOVARTIS AG

  公开号：WO1997016452A1

  公开（公告）日：1997-05-09

  (EN) 2-Amino-6-anilino-purine derivatives of formula (1) in which the symbols are as defined in claim 1, are described. These compounds inhibit p34cdc2/cyclin Bcdc13 kinase and can be used for treatment of hyperproliferative diseases, for example tumour diseases.(FR) On décrit des dérivés 2-amino-6-anilino-purines de la formule 1 dans laquelle les symboles sont tels que définis dans la revendication 1. Ces composés inhibent la p34cdc2/cycline Bcdc13 kinase et on peut les utiliser dans le traitement de maladies à hyperprolifération, par exemple des tumeurs.

  (中文) 描述了式（1）中符号如权利要求1所定义的2-氨基-6-苯胺基嘌呤衍生物。这些化合物抑制p34cdc2 / cyclin Bcdc13激酶，可用于治疗增生性疾病，例如肿瘤疾病。
• Purine derivatives and processes for their preparation
  申请人：Novartis AG

  公开号：US07091346B1

  公开（公告）日：2006-08-15

  2-Amino-6-anilino-purine derivatives of the formula 1 in which the symbols are as defined in claim 1 are described. These compounds inhibit p34cdc2/cyclin Bcdc13 kinase and can be used for treatment of hyperproliferative diseases, for example tumour diseases.

  描述了公式1中符号定义如权利要求1所述的2-氨基-6-苯胺基嘌呤衍生物。这些化合物抑制p34cdc2 / cyclin Bcdc13激酶，可用于治疗过度增殖性疾病，例如肿瘤疾病。
• Dual CLK/CDK1 inhibitors for cancer treatment
  申请人：SRI INTERNATIONAL

  公开号：US10722515B2

  公开（公告）日：2020-07-28

  The disclosure generally relates to substituted purine analogs that are dual CLK2/CDK1 inhibitors or more potent and specific CLK inhibitors to target CLK2 and CDK1 kinases. These compounds may be useful in the treatment of germ-line mutations of the spliceosome leading to the development of cancers and other human disease. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本公开内容一般涉及取代的嘌呤类似物，它们是 CLK2/CDK1 双重抑制剂或更强效、更特异的 CLK 抑制剂，可靶向 CLK2 和 CDK1 激酶。这些化合物可用于治疗导致癌症和其他人类疾病的剪接体种系突变。本摘要旨在作为一种扫描工具，用于在特定技术领域进行搜索，并非对本发明的限制。