Cdk1/2抑制剂III | 443798-47-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: Cdk1/2抑制剂III
• 英文名称: CDK1/2 inhibitor III
• 英文别名: 5-amino-N-(2,6-difluorophenyl)-3-((4-sulfamoylphenyl)amino)-1H-1,2,4-triazole-1-carbothioamide；5-amino-N-(2,6-difluorophenyl)-3-(4-sulfamoylanilino)-1,2,4-triazole-1-carbothioamide
• CAS: 443798-47-8；443798-55-8
• 化学式: C₁₅H₁₃F₂N₇O₂S₂
• 分子量: 425.443
• InChiKey: ARIOBGGRZJITQX-UHFFFAOYSA-N

物化性质

• 沸点：
  649.1±65.0 °C(Predicted)
• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  181
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  phenyl-N'-cyano-N-(4-sulfamoylphenyl)carbamimidate 在 sodium hydroxide 、 肼 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 Cdk1/2抑制剂III
  参考文献：
  名称：

  1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogues as Novel and Potent Anticancer Cyclin-Dependent Kinase Inhibitors:  Synthesis and Evaluation of Biological Activities

  摘要：

  A series of 1-acyl-1H-[1,2,4]triazole-3,5-diamine analogues were synthesized as cyclin-dependent kinase (CDK) inhibitors. These compounds showed potent and selective CDK1 and CDK2 inhibitory activities and inhibited in vitro cellular proliferation in various human tumor cells. Representative compound 3b demonstrated in vivo efficacy in a human melanoma A375 xenograft model in nude mice.

  DOI：

  10.1021/jm050267e

文献信息

• BENZIMIDAZOLE-2-PIPERAZINE HETEROCYCLIC COMPOUND, PHARMACEUTICAL COMPOSITION CONTAINING THE SAME, PREPARATION METHOD AND USE THEREOF
  申请人：SHANGHAI HUILUN LIFE SCIENCE & TECHNOLOGY CO., LTD

  公开号：US20160159776A1

  公开（公告）日：2016-06-09

  The present invention relates to a class of benzimidazole-2-piperazine heterocyclic derivatives, a preparation method and medical use thereof. Specifically, the present invention relates to a new benzimidazole-2-piperazine heterocyclic derivative of general Formula (I), a preparation method, a pharmaceutical composition containing the same, and use thereof as a therapeutic agent and especially as a poly(ADP-ribose)polymerase (PARP) inhibitor.

  本发明涉及一类苯并咪唑-2-哌嗪杂环衍生物、其制备方法及其医疗用途。具体而言，本发明涉及一种通式（I）的新苯并咪唑-2-哌嗪杂环衍生物、其制备方法、含有该衍生物的药物组合物，以及作为治疗剂特别是作为聚（ADP-核糖）聚合酶（PARP）抑制剂的用途。
• Substituted triazole diamine derivatives as kinase inhibitors
  申请人：——

  公开号：US20040077699A1

  公开（公告）日：2004-04-22

  The present invention provides substituted triazole diamine derivatives as selective kinase or dual-kinase inhibitors and a method for treating or ameliorating a selective kinase or dual-kinase mediated disorder.

  本发明提供了取代三唑二胺衍生物作为选择性激酶或双激酶抑制剂，并提供了用于治疗或改善选择性激酶或双激酶介导的疾病的方法。
• In silico Screening and Evaluation of<i>Plasmodium falciparum</i>Protein Kinase 5 (PK5) Inhibitors
  作者：Amber L. Eubanks、Marisha M. Perkins、Kayla Sylvester、Jack G. Ganley、Dora Posfai、Paul C. Sanschargrin、Jiyong Hong、Piotr Sliz、Emily R. Derbyshire

  DOI：10.1002/cmdc.201800625

  日期：2018.12.6

  commercially available compounds was conducted with an unbiased approach to identify potential malaria inhibitors that bind to the Plasmodium falciparum protein kinase 5 (PfPK5) ATP‐binding site. PfPK5 is a cyclin‐dependent kinase‐like protein with high sequence similarity to human cyclin‐dependent kinase 2 (HsCDK2), but its precise role in cell‐cycle regulation remains unclear. After two‐dimensional fingerprinting

  使用无偏方法对35万种市售化合物进行了计算机筛选，以鉴定与恶性疟原虫蛋白激酶5（Pf PK5）ATP结合位点结合的潜在疟疾抑制剂。P f PK5是一种细胞周期蛋白依赖性激酶样蛋白，与人细胞周期蛋白依赖性激酶2（Hs CDK2）具有高度序列相似性，但其在细胞周期调控中的确切作用尚不清楚。在对得分最高的化合物进行二维指纹图谱分析后，根据其结构多样性对182种候选化合物进行了生化测试的优先级排序。对这些化合物的评估表明，135与Pf PK5的结合程度与已知Pf相似或更好。PK5抑制剂，证实该文库富含Pf PK5结合化合物。分别选择了先前报道的三唑二胺Hs CDK2抑制剂和筛选出的4-甲基伞形酮进行类似物研究。这项研究的结果强调优化难以兼顾Pf的用于PK5亲和力和结合选择性Pf的PK5超过其最接近人类同源HS CDK2。我们的方法能够通过适度的筛选活动发现几种新的Pf PK5结合化合物，并揭示了第一个具有改善的Pf
• METHODS, COMPOSITIONS AND KITS FOR PROMOTING MOTOR NEURON SURVIVAL AND TREATING AND DIAGNOSING NEURODEGENERATIVE DISORDERS
  申请人：PRESIDENT AND FELLOWS OF HARVARD COLLEGE

  公开号：US20160082015A1

  公开（公告）日：2016-03-24

  Methods, compositions, and kits for promoting motor neuron survival and for treatment and diagnosis of neurodegenerative disorders such as Amyotrophic lateral sclerosis (ALS) and Spinal muscular atrophy (SMA) are described herein.

  本文描述了促进运动神经元存活以及治疗和诊断神经退行性疾病，如肌萎缩侧索硬化症（ALS）和脊髓性肌萎缩症（SMA）的方法、组合物和试剂盒。
• Benzimidazole-2-piperazine heterocyclic compound, pharmaceutical composition containing the same, preparation method and use thereof
  申请人：Shanghai Huilun Life Science & Technology Co., Ltd.

  公开号：US10196381B2

  公开（公告）日：2019-02-05

  The present invention relates to a class of benzimidazole-2-piperazine heterocyclic derivatives, a preparation method and medical use thereof. Specifically, the present invention relates to a new benzimidazole-2-piperazine heterocyclic derivative of general Formula (I), a preparation method, a pharmaceutical composition containing the same, and use thereof as a therapeutic agent and especially as a poly(ADP-ribose)polymerase (PARP) inhibitor.

  本发明涉及一类苯并咪唑-2-哌嗪杂环衍生物、其制备方法和医疗用途。具体而言，本发明涉及通式（I）的一种新的苯并咪唑-2-哌嗪杂环衍生物、制备方法、含有该衍生物的药物组合物，以及其作为治疗剂，特别是作为聚（ADP-核糖）聚合酶（PARP）抑制剂的用途。