methyl 7-(4-aminobenzamido)heptanoate | 1036742-49-0

• 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 7-(4-aminobenzamido)heptanoate
• 英文别名: Methyl 7-[(4-aminobenzoyl)amino]heptanoate
• CAS: 1036742-49-0
• 化学式: C₁₅H₂₂N₂O₃
• 分子量: 278.351
• InChiKey: ZKGOUPABPCYKOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  81.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 7-(4-aminobenzamido)heptanoate 在 potassium cyanide 、 tetrakis(actonitrile)copper(I) hexafluorophosphate 、 羟胺 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三[(1-苄基-1H-1,2,3-三唑-4-基)甲基]胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 17.0h， 生成 FITC-4-(((1-(3-aminopropyl)-1H-1,2,3-triazol-4-yl)methyl)amino)-N-(7-(hydroxy-amino)-7-oxoheptyl)benzamide
  参考文献：
  名称：

  Class I/IIb-Selective HDAC Inhibitor Exhibits Oral Bioavailability and Therapeutic Efficacy in Acute Myeloid Leukemia

  摘要：

  The HDAC inhibitor 4-tert-butyl-N-(4-(hydroxycarbamoyl)phenyl)benzamide (AES-350, 51) was identified as a promising preclinical candidate for the treatment of acute myeloid leukemia (AML), an aggressive malignancy with a meagre 24% 5-year survival rate. Through screening of low-molecular-weight analogues derived from the previously discovered novel HDAC inhibitor, AES-135, compound 51 demonstrated greater HDAC isoform selectivity, higher cytotoxicity in MV4-11 cells, an improved therapeutic window, and more efficient absorption through cellular and lipid membranes. Compound 51 also demonstrated improved oral bioavailability compared to SAHA in mouse models. A broad spectrum of experiments, including FACS, ELISA, and Western blotting, were performed to support our hypothesis that 51 dose-dependently triggers apoptosis in AML cells through HDAC inhibition.

  DOI：

  10.1021/acsmedchemlett.9b00471
• 作为产物：
  描述：

  7-(4-nitrobenzoylamino)-heptanoic acid methyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以97%的产率得到methyl 7-(4-aminobenzamido)heptanoate
  参考文献：
  名称：

  开发基于荧光偏振的组蛋白去乙酰化酶配体发现分析。

  摘要：

  组蛋白去乙酰化酶 (HDAC) 调节许多重要的生理过程，调节 HDAC 活性的小分子的发现具有学术和临床意义。HDAC 抑制剂，尤其是 SAHA，已被用作癌症化学治疗剂，但可用于治疗精神障碍、疟疾和其他疾病。在此，我们描述了一种基于荧光偏振的廉价且稳健的检测，用于 HDAC 配体发现。该测定非常适合高通量筛选和酶动力学研究。

  DOI：

  10.1016/j.bmcl.2008.04.007

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.