N2-(顺-2-氨基环己基)-N6-(3-氯苯基)-9-乙基-9H-嘌呤-2,6-二胺 | 190653-73-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: N2-(顺-2-氨基环己基)-N6-(3-氯苯基)-9-乙基-9H-嘌呤-2,6-二胺
• 英文名称: N²-(cis-2-aminocyclohexyl)-N⁶-(3-chlorophenyl)-9-ethyl-9H-purine-2,6-diamine
• 英文别名: CGP-74514A；9H-Purine-2,6-diamine, N2-(2-aminocyclohexyl)-N6-(3-chlorophenyl)-9-ethyl-, cis-；2-N-[(1R,2S)-2-aminocyclohexyl]-6-N-(3-chlorophenyl)-9-ethylpurine-2,6-diamine
• CAS: 190653-73-7
• 化学式: C₁₉H₂₄ClN₇
• 分子量: 385.899
• InChiKey: UTBSBSOBZHXMHI-LSDHHAIUSA-N

物化性质

• 沸点：
  618.7±65.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  93.7
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 N2-(顺-2-氨基环己基)-N6-(3-氯苯基)-9-乙基-9H-嘌呤-2,6-二胺 在 碳酸氢钠 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 以31%的产率得到N-cis(2-((6-((3-chlorophenyl)amino)-9-ethyl-9H-purin-2-yl)amino)cyclohexyl)acetamide
  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 potassium carbonate 、 三乙胺 作用下， 以 N-甲基吡咯烷酮 、 二甲基亚砜 、 正丁醇 为溶剂， 反应 152.0h， 生成 N2-(顺-2-氨基环己基)-N6-(3-氯苯基)-9-乙基-9H-嘌呤-2,6-二胺
  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

文献信息

• [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。
• METHOD OF BLOCKING TRANSMISSION OF MALARIAL PARASITE
  申请人：THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERV

  公开号：US20160264570A1

  公开（公告）日：2016-09-15

  The invention provides a method of blocking transmission of a Plasmodium parasite and a method of treating or preventing malaria comprising administering to an animal an effective amount of a first compound of formula I: wherein A, B, R 1 , R 2 , R 10 , and R 11 are described herein, either alone or in combination with a second compound selected from elesclomol, NSC 174938, NVP-AUY922, Maduramicin, Narasin, Alvespimycin, Omacetaxine, Thiram, Zinc pyrithione, Phanquinone, Bortezomib, Salinomycin sodium, Monensin sodium, Dipyrithione, Dicyclopentamethylene-thiuram disulfide, YM155, Withaferin A, Adriamycin, Romidepsin, AZD-1 152-HQPA, CAY10581, Plicamycin, CUDC-101, Auranofin, Trametinib, GSK-458, Afatinib, and Panobinostat.

  本发明提供了一种阻止疟原虫传播的方法和一种治疗或预防疟疾的方法，包括向动物施用公式I的第一化合物的有效量，其中A、B、R1、R2、R10和R11如本文所述，可以单独使用或与从elesclomol、NSC 174938、NVP-AUY922、Maduramicin、Narasin、Alvespimycin、Omacetaxine、Thiram、Zinc pyrithione、Phanquinone、Bortezomib、Salinomycin sodium、Monensin sodium、Dipyrithione、Dicyclopentamethylene-thiuram disulfide、YM155、Withaferin A、Adriamycin、Romidepsin、AZD-1 152-HQPA、CAY10581、Plicamycin、CUDC-101、Auranofin、Trametinib、GSK-458、Afatinib和Panobinostat中选择的第二化合物组合使用。
• Measurement method using biosensor
  申请人：FUJI PHOTO FILM CO., LTD.

  公开号：EP1739427A1

  公开（公告）日：2007-01-03

  It is an object of the present invention to provide a method for carrying out on a same biosensor both of the measurement of the amount of a physiologically active substance immobilized on a biosensor substrate and the measurement of the biological activity of the above physiologically active substance, thereby analyzing the interaction of a substance with the above physiologically active substance that maintains its activity. The present invention provides a measurement method using a biosensor substrate, wherein both the amount of a physiologically active substance immobilized on the substrate and the biological activity of the physiologically active substance immobilized on the substrate are measured on said same biosensor substrate.

  本发明的目的是提供一种在同一个生物传感器上同时进行固定在生物传感器基底上的生理活性物质的量的测量和上述生理活性物质的生物活性的测量的方法，从而分析一种物质与上述生理活性物质的相互作用，保持其活性。本发明提供了一种使用生物传感器基底的测量方法，其中固定在基底上的生理活性物质的量和固定在基底上的生理活性物质的生物活性都是在所述同一生物传感器基底上测量的。
• METHOD FOR THE DIAGNOSIS, PROGNOSIS AND TREATMENT OF BREAST CANCER METASTASIS
  申请人：Fundació Privada Institut de Recerca Biomèdica

  公开号：EP2626431A2

  公开（公告）日：2013-08-14

  The present invention relates to a method for the diagnosis or the prognosis of metastasis in breast cancer which comprises determining if the c-MAF gene is amplified in a primary tumor sample. Likewise, the invention also relates to a method for the diagnosis or the prognosis of metastasis in ER- breast cancer, as well as to a method for determining the tendency to develop bone metastasis with respect to metastasis in other organs, which comprise determining the c-MAF gene expression level. Finally, the invention relates to the use of a c-MAF inhibitor as therapeutic target for treating the ER- breast cancer metastasis.

  本发明涉及一种诊断或预后乳腺癌转移的方法，该方法包括确定原发肿瘤样本中 c-MAF 基因是否扩增。同样，本发明还涉及一种诊断或预后ER-乳腺癌转移的方法，以及一种确定骨转移与其他器官转移倾向的方法，其中包括确定c-MAF基因的表达水平。最后，本发明涉及使用 c-MAF 抑制剂作为治疗 ER- 乳腺癌转移的治疗靶点。