N-(2-aminophenyl)-4-(2-methyl-2-phenylpropanamido)benzamide | 854780-06-6

• 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-aminophenyl)-4-(2-methyl-2-phenylpropanamido)benzamide
• 英文别名: N-(2-aminophenyl)-4-[(2-methyl-2-phenylpropanoyl)amino]benzamide
• CAS: 854780-06-6
• 化学式: C₂₃H₂₃N₃O₂
• 分子量: 373.455
• InChiKey: PWRJEWJFZSGGQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  84.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  methyl 4-(2-methyl-2-phenylpropanamido)benzoate 在 水 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 N-(2-aminophenyl)-4-(2-methyl-2-phenylpropanamido)benzamide
  参考文献：
  名称：

  Targeting breast cancer stem cells by novel HDAC3-selective inhibitors

  摘要：

  Although histone deacetylase (HDAC) inhibitors have been known to suppress the cancer stem cell (CSC) population in multiple types of cancer cells, it remains unclear which HDAC isoforms and corresponding mechanisms contribute to this anti-CSC activity. Pursuant to our previous finding that HDAC8 regulates CSCs in triple-negative breast cancer (TNBC) cells by targeting Notch1 stability, we investigated related pathways and found HDAC3 to be mechanistically linked to CSC homeostasis by increasing beta-catenin expression through the Akt/GSM3 beta pathway. Accordingly, we used a pan-HDAC inhibitor, AR-42 (1), as a scaffold to develop HDAC3-selective inhibitors, obtaining the proof-of-concept with 18 and 28. These two derivatives exhibited high potency and isoform selectivity in HDAC3 inhibition. Equally important, they showed in vitro and/or in vivo efficacy in suppressing the CSC subpopulation of TNBC cells via the downregulation of beta-catenin. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.08.069

文献信息

• Zn2Motif-Tethered Short-Chain Fatty Acids as a Novel Class of Histone Deacetylase
  申请人：Chen Ching-Shih

  公开号：US20070225373A1

  公开（公告）日：2007-09-27

  Zn 2+ -chelating motif-tethered fatty acids as histone deacetylase (HDAC) inhibitors. One hydroxamate-tethered phenylbutyrate compound, N-hydroxy-4-(4-phenylbutyrylamino)-benzamide (HTPB), displayed nM potency in inhibiting HDAC activity. Exposure of several cancer cell lines to HTPB at sub-μM concentrations showed reduced cell proliferation accompanied by histone hyperacetylation and elevated p21 WAF/CIP1 expression, hallmark features associated with intracellular HDAC inhibition.

  Zn2+螯合基固定的脂肪酸作为组蛋白去乙酰化酶（HDAC）抑制剂。一种羟酰胺基固定的苯丁酸化合物，N-羟基-4-(4-苯丁酰氨基)-苯甲酰胺（HTPB），在抑制HDAC活性方面表现出纳摩尔级别的效力。将几种癌细胞系暴露于亚微米浓度的HTPB中，显示出细胞增殖减少，伴随着组蛋白高乙酰化和升高的p21WAF/CIP1表达，这是与细胞内HDAC抑制相关的标志性特征。
• ZN2+Chelating Motif-Tethered Short-Chain Fatty Acids as a Novel Class of Histone Deacetylase Inhibitors
  申请人：Chen Ching-Shih

  公开号：US20090137679A1

  公开（公告）日：2009-05-28

  Zn 2+ -chelating motif-tethered fatty acids as histone deacetylase (HDAC) inhibitors. Compounds performed well in in vitro and in vivo tests.

  以Zn2+螯合基固定的脂肪酸作为组蛋白去乙酰化酶（HDAC）抑制剂。该化合物在体外和体内测试中表现良好。
• ZN 24 -CHELATING MOTIF-TETHERED SHORT-CHAIN FATTY ACIDS AS A NOVEL CLASS OF HISTONE DEACETYLASE INHIBITORS
  申请人：THE OHIO STATE UNIVERSITY RESEARCH FOUNDATION

  公开号：EP1696898A2

  公开（公告）日：2006-09-06
• ZN 2+ -CHELATING MOTIF-TETHERED SHORT-CHAIN FATTY ACIDS AS A NOVEL CLASS OF HISTONE DEACETYLASE INHIBITORS
  申请人：The Ohio State University Research Foundation

  公开号：EP1696898B1

  公开（公告）日：2015-11-18
• COMPOSITIONS AND METHODS FOR REDUCING PROLIFERATION AND VIABILITY OF LYMPHOBLASTOID CELLS
  申请人：Baiocchi Robert A.

  公开号：US20110281950A1

  公开（公告）日：2011-11-17

  Pharmaceutical compositions including an HDAC inhibitor and a pharmaceutically acceptable carrier wherein the HDAC inhibitor is present in an amount sufficient to achieve a plasma concentration from about 100 nM to about 2 uM and methods of treatment using the same. Pharmaceutical compositions including an HDAC inhibitor and a pharmaceutically acceptable carrier wherein the HDAC inhibitor is present in an amount from 0.1 mg to 100 mg. Pharmaceutical compositions including an HDAC inhibitor and a pharmaceutically acceptable carrier, wherein the concentration of the HDAC inhibitor is sufficient to decrease the relative viability of lymphoblastoid cells by at least about 50 percent and/or is sufficient to decrease the proliferation of lymphoblastoid cells by at least about 60 percent and/or is sufficient to decrease the relative viability of peripheral blood mononuclear cells by less than about 50 percent and methods of treatment using the same.