N²-((1R,2R)-2-aminocyclohexyl)-N⁶-(3-chlorophenyl)-9-ethyl-9H-purine-2,6-diamine | 190654-04-7

• 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: N²-((1R,2R)-2-aminocyclohexyl)-N⁶-(3-chlorophenyl)-9-ethyl-9H-purine-2,6-diamine
• 英文别名: N2-[(1R,2S)-2-Aminocyclohexyl]-N6-(3-chlorophenyl)-9-ethyl-9H-purine-2,6-diamine；2-N-[(1R,2R)-2-aminocyclohexyl]-6-N-(3-chlorophenyl)-9-ethylpurine-2,6-diamine
• CAS: 190654-04-7
• 化学式: C₁₉H₂₄ClN₇
• 分子量: 385.899
• InChiKey: UTBSBSOBZHXMHI-HUUCEWRRSA-N

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

• 作为产物：
  描述：

  2,6-dichloro-9-ethyl-9H-purine 在 三乙胺 作用下， 以 N-甲基吡咯烷酮 、 正丁醇 为溶剂， 反应 32.0h， 生成 N²-((1R,2R)-2-aminocyclohexyl)-N⁶-(3-chlorophenyl)-9-ethyl-9H-purine-2,6-diamine
  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。
• 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。
• PURINE DERIVATIVES AND PROCESSES FOR THEIR PREPARATION
  申请人：Novartis AG

  公开号：EP0874846B1

  公开（公告）日：2003-04-02
• DUAL CLK/CDK1 INHIBITORS FOR CANCER TREATMENT
  申请人：SRI INTERNATIONAL

  公开号：US20190255059A1

  公开（公告）日：2019-08-22

  This disclosure generally relates to dual CLK2/CDK1 inhibitors or more potent and specific CLK inhibitors to target CLK2 and CDK1 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.