methyl 8-((2-aminophenyl)amino)-8-oxooctanoate | 1449690-49-6

• 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: methyl 8-((2-aminophenyl)amino)-8-oxooctanoate
• CAS: 1449690-49-6
• 化学式: C₁₅H₂₂N₂O₃
• 分子量: 278.351
• InChiKey: INZLRQRPAHZQCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.72
• 重原子数：
  20.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  81.42
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl 8-((2-aminophenyl)amino)-8-oxooctanoate 在 溶剂黄146 作用下， 以 甲苯 为溶剂， 生成
  参考文献：
  名称：

  Identification of novel HDAC inhibitors through cell based screening and their evaluation as potential anticancer agents

  摘要：

  A series of benzimidazole based HDAC inhibitors have been rationally designed, synthesized and screened. The SAR of this new chemotype is described. The lead compound, 11e, showed strong activity in several cellular assays and demonstrated in vivo efficacy in mouse xenograft pancreatic cancer models. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.001
• 作为产物：
  描述：

  2-硝基苯基氨基甲酸叔丁酯 在 盐酸 、 铁粉 、 氯化铵 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 14.0h， 生成 methyl 8-((2-aminophenyl)amino)-8-oxooctanoate
  参考文献：
  名称：

  N-alkyl-hydroxybenzoyl anilide hydroxamates as dual inhibitors of HDAC and HSP90, downregulating IFN-γ induced PD-L1 expression

  摘要：

  Novel dual inhibitors of histone deacetylase (HDAC) and heat-shock protein 90 (HSP90) are synthesized and evaluated. These compounds are endowed with potent HDAC and HSP90 inhibitory activities with IC50 values in nanomolar range with Compound 20 (HDAC IC50 =194 nM: HSP90ce IC50 =153 nM) and compound 26 (HDAC IC50- 360 nM; HSP90 alpha IC50 W 77 nM) displaying most potent HDAC and HSP90a inhibitory activities. Both of these compounds induce HSP70 expression and down regulate HSP90 client proteins which play important roles in the regulation of survival and invasiveness in cancer cells. In addition, compounds 20 and 26 induce acetylation of alpha-tubulin and histone H3. Significantly, compounds 20 and 26 could effectively reduce programmed death-ligand 1 (PD-L1) expression in IFN-gamma treated lung H1975 cells in a dose dependent manner. These findings suggest that dual inhibition of HDAC and HSP90 that can modulate immunosuppressive ability of tumor area may provide a better therapeutic strategy for cancer treatment in the future. (C) 2019 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2019.111725

文献信息

• Discovery of <i>N</i>1-(4-((7-Cyclopentyl-6-(dimethylcarbamoyl)-7<i>H</i>-pyrrolo[2,3-<i>d</i>]pyrimidin-2-yl)amino)phenyl)-<i>N</i>8-hydroxyoctanediamide as a Novel Inhibitor Targeting Cyclin-dependent Kinase 4/9 (CDK4/9) and Histone Deacetlyase1 (HDAC1) against Malignant Cancer
  作者：Yongtao Li、Xiaohe Luo、Qingxiang Guo、Yongwei Nie、Tianqi Wang、Chao Zhang、Zhi Huang、Xin Wang、Yanhua Liu、Yanan Chen、Jianyu Zheng、Shengyong Yang、Yan Fan、Rong Xiang

  DOI：10.1021/acs.jmedchem.8b00209

  日期：2018.4.12

  A series of novel, highly potent, selective inhibitors targeting both CDK4/9 and HDAC1 have been designed and synthesized. N1-(4-((7-Cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo [2,3-d]pyrimidin-2-yl)amino)phenyl)-N8-hydroxyo ctan ediamide (6e) was discovered. The lead compound 6e with excellent CDK4/9 and HDAC1 inhibitory activity of IC50 = 8.8, 12, and 2.2 nM, respectively, can effectively induce apoptosis of cancer cell lines. The kinase profiling of compound 6e showed excellent selectivity and specificity. Compound 6e induces G2/M arrest in high concentration and G0/G1 arrest in low concentration to prevent the proliferation and differentiation of cancer cells. Mice bared-breast cancer treated with 6e showed significant antitumor efficacy. The insight into mechanisms of 6e indicated that it could induce cancer cell death via cell apoptosis based on CDK4/9 and HDAC1 repression and phosphorylation of p53. Our data demonstrated the novel compound 6e could be a promising drug candidate for cancer therapy.