N-(2-Amino-phenyl)-4-[(9-butyl-2-chloro-9H-purin-6-ylamino)-methyl]-benzamide | 503042-85-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-Amino-phenyl)-4-[(9-butyl-2-chloro-9H-purin-6-ylamino)-methyl]-benzamide
• 英文别名: N-(2-aminophenyl)-4-[[(9-butyl-2-chloropurin-6-yl)amino]methyl]benzamide
• CAS: 503042-85-1
• 化学式: C₂₃H₂₄ClN₇O
• 分子量: 449.943
• InChiKey: JGWMPVCHPKBZAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,6-二氯嘌呤 在 水 、 potassium carbonate 、 (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 、 正丁醇 为溶剂， 反应 6.17h， 生成 N-(2-Amino-phenyl)-4-[(9-butyl-2-chloro-9H-purin-6-ylamino)-methyl]-benzamide
  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

• Inhibitors of histone deacetylase
  申请人：Delorme Daniel

  公开号：US20050288282A1

  公开（公告）日：2005-12-29

  The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

  这项发明涉及抑制组蛋白去乙酰化酶。该发明提供了抑制组蛋白去乙酰化酶酶活性的化合物和方法。该发明还提供了用于治疗细胞增殖性疾病和症状的组合物和方法。
• Design and synthesis of 4-[(s-triazin-2-ylamino)methyl]-N-(2-aminophenyl)-benzamides and their analogues as a novel class of histone deacetylase inhibitors
  作者：Isabelle Paquin、Stéphane Raeppel、Silvana Leit、Frédéric Gaudette、Nancy Zhou、Oscar Moradei、Oscar Saavedra、Naomy Bernstein、Franck Raeppel、Giliane Bouchain、Sylvie Fréchette、Soon H. Woo、Arkadii Vaisburg、Marielle Fournel、Ann Kalita、Marie-France Robert、Aihua Lu、Marie-Claude Trachy-Bourget、Pu Theresa Yan、Jianhong Liu、Jubrail Rahil、A. Robert MacLeod、Jeffrey M. Besterman、Zuomei Li、Daniel Delorme

  DOI：10.1016/j.bmcl.2007.12.009

  日期：2008.2

  Inhibition of histone deacetylases (HDAC) is emerging as a new strategy in human cancer therapy. The synthesis and biological evaluation of a variety of 4-(heteroaryl aminomethyl)-N-(2-aminophenyl)-benzamides is presented herein. From the different series bearing a six-membered heteroaromatic ring studied, the s-triazine series showed the best HDAC1 enzyme and in vitro anti-proliferative activities with IC50 values below micromolar range. Some of these compounds can also significantly reduce tumor growth in human tumor xenograft models in mice. (C) 2007 Elsevier Ltd. All rights reserved.
• US6897220B2
  申请人：——

  公开号：US6897220B2

  公开（公告）日：2005-05-24
• US7595343B2
  申请人：——

  公开号：US7595343B2

  公开（公告）日：2009-09-29
• US7838520B2
  申请人：——

  公开号：US7838520B2

  公开（公告）日：2010-11-23