methyl 4-[[(2-chloro-9-cyclopentyl-9H-purin-6-yl)-amino]-methyl]-benzoate | 310400-94-3

• 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: methyl 4-[[(2-chloro-9-cyclopentyl-9H-purin-6-yl)-amino]-methyl]-benzoate
• 英文别名: Methyl 4-[[(2-chloro-9-cyclopentylpurin-6-yl)amino]methyl]benzoate
• CAS: 310400-94-3
• 化学式: C₁₉H₂₀ClN₅O₂
• 分子量: 385.853
• InChiKey: PZIFZFDZDLEJLO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  81.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 4-[[(2-chloro-9-cyclopentyl-9H-purin-6-yl)-amino]-methyl]-benzoate 在 水 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.17h， 生成 N1-(4-(((2-chloro-9-cyclopentyl-9H-purin-6-yl)amino)methyl)phenyl)benzene-1,2-diamine
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel histone deacetylase1/2 (HDAC1/2) and cyclin-dependent Kinase2 (CDK2) dual inhibitors against malignant cancer

  摘要：

  In the current study, we have designed and synthesized a series of novel histone deacetylase1/2 (HDAC1/2) and cyclin-dependent kinase2 (CDK2) dual inhibitors by integrating purine-based pharmacophore into the recognition cap group of CS055. The representative compound 14d with excellent anti-proliferative activities towards five solid cancer cells, showed potent inhibitory activities against HDAC1, HDAC2 and CDK2 with IC50 values of 70.7 nM, 23.1 nM and 0.80 mu M, respectively. Besides, compound 14d could effectively block the cell cycle in the G2/M phase and induce apoptosis, which might be related to increasing intracellular ROS levels. Importantly, compound 14d exhibited desirable pharmacokinetic (PK) properties with the intraperitoneal bioavailability of 50.8% in ICR mice, and potent in vivo antitumor activity in the HCT116 xenograft model. Therefore, compound 14d could be considered as a promising lead compound for the development of multitargeting anticancer agents. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112322
• 作为产物：
  描述：

  2,6-二氯嘌呤 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 4.0h， 生成 methyl 4-[[(2-chloro-9-cyclopentyl-9H-purin-6-yl)-amino]-methyl]-benzoate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel histone deacetylase1/2 (HDAC1/2) and cyclin-dependent Kinase2 (CDK2) dual inhibitors against malignant cancer

  摘要：

  In the current study, we have designed and synthesized a series of novel histone deacetylase1/2 (HDAC1/2) and cyclin-dependent kinase2 (CDK2) dual inhibitors by integrating purine-based pharmacophore into the recognition cap group of CS055. The representative compound 14d with excellent anti-proliferative activities towards five solid cancer cells, showed potent inhibitory activities against HDAC1, HDAC2 and CDK2 with IC50 values of 70.7 nM, 23.1 nM and 0.80 mu M, respectively. Besides, compound 14d could effectively block the cell cycle in the G2/M phase and induce apoptosis, which might be related to increasing intracellular ROS levels. Importantly, compound 14d exhibited desirable pharmacokinetic (PK) properties with the intraperitoneal bioavailability of 50.8% in ICR mice, and potent in vivo antitumor activity in the HCT116 xenograft model. Therefore, compound 14d could be considered as a promising lead compound for the development of multitargeting anticancer agents. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112322

文献信息

• Derivatives of purine, their preparation process and pharmaceutical compositions containing them
  申请人：Haesslein Jean-Luc

  公开号：US20050187228A1

  公开（公告）日：2005-08-25

  A compound of the formula wherein R is defined as in the specification, which compounds have an inhibitory effect vis-à-vis cycline-dependent kinase proteins (cdk) and are endowed with antimitotic properties.

  其中R在规范中定义，该化合物具有对细胞周期依赖性激酶蛋白（cdk）具有抑制作用并具有抗有丝分裂特性。
• US7122669B1
  申请人：——

  公开号：US7122669B1

  公开（公告）日：2006-10-17
• US7208598B2
  申请人：——

  公开号：US7208598B2

  公开（公告）日：2007-04-24
• Design, synthesis and biological evaluation of novel histone deacetylase1/2 (HDAC1/2) and cyclin-dependent Kinase2 (CDK2) dual inhibitors against malignant cancer
  作者：Fan Yun、Chunhui Cheng、Sadeeq Ullah、Qipeng Yuan

  DOI：10.1016/j.ejmech.2020.112322

  日期：2020.7

  In the current study, we have designed and synthesized a series of novel histone deacetylase1/2 (HDAC1/2) and cyclin-dependent kinase2 (CDK2) dual inhibitors by integrating purine-based pharmacophore into the recognition cap group of CS055. The representative compound 14d with excellent anti-proliferative activities towards five solid cancer cells, showed potent inhibitory activities against HDAC1, HDAC2 and CDK2 with IC50 values of 70.7 nM, 23.1 nM and 0.80 mu M, respectively. Besides, compound 14d could effectively block the cell cycle in the G2/M phase and induce apoptosis, which might be related to increasing intracellular ROS levels. Importantly, compound 14d exhibited desirable pharmacokinetic (PK) properties with the intraperitoneal bioavailability of 50.8% in ICR mice, and potent in vivo antitumor activity in the HCT116 xenograft model. Therefore, compound 14d could be considered as a promising lead compound for the development of multitargeting anticancer agents. (C) 2020 Elsevier Masson SAS. All rights reserved.