7-(3-氨基苯基氨基甲酰基)庚酸甲酯 | 1204005-97-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 7-(3-氨基苯基氨基甲酰基)庚酸甲酯
• 英文名称: methyl 8-((3-aminophenyl)amino)-8-oxooctanoate
• 英文别名: Methyl 8-(3-aminophenylamino)-8-oxooctanoate；methyl 8-(3-aminoanilino)-8-oxooctanoate
• CAS: 1204005-97-9
• 化学式: C₁₅H₂₂N₂O₃
• 分子量: 278.351
• InChiKey: GLTYVYZZMKMYLU-UHFFFAOYSA-N

物化性质

• 沸点：
  480.9±30.0 °C(Predicted)
• 密度：
  1.141±0.06 g/cm3(Predicted)

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：

  7-(3-氨基苯基氨基甲酰基)庚酸甲酯 在 溶剂黄146 、 sodium nitrite 、 sodium azide 作用下， 以 水 为溶剂， 反应 1.5h， 以0.28 g的产率得到7-(3-azidophenylcarbamoyl)heptanoic acid methyl ester
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Triazol-4-ylphenyl-Bearing Histone Deacetylase Inhibitors as Anticancer Agents

  摘要：

  Our triazole-based histone deacetylase inhibitor (HDACI), octanedioic acid hydroxyamide[3-(1-phenyl-1H-[1,2,3]triazol-4-yl)phenyl]amide (4a), suppresses pancreatic cancer cell growth in vitro with the lowest IC50 value of 20 nM against MiaPaca-2 cell. In this study, we continued our efforts to develop triazol-4-ylphenyl bearing hydroxamate analogues by embellishing the terminal phenyl ring of 4a with different substituents. The isoform inhibitory profile of these hydroxamate analogues was similar to those of 4a. All of these triazol-4-ylphenyl bearing hydroxamates are pan-HDACIs like SAHA. Moreover, compounds 4h and 11a were found to be very effective inhibitors of cancer cell growth in the HupT3 (IC50 = 50 nM) and MiaPaca-2 (IC50 = 40 nM) cancer cell lines, respectively. Compound 4a was found to reactivate the expression of CDK inhibitor proteins and to suppress pancreatic cancer cell growth in vivo. Taken together, these data further support the value of the triazol-4-ylphenyl bearing hydroxamates in identifying potential pancreatic cancer therapies.

  DOI：

  10.1021/jm901667k
• 作为产物：
  描述：

  methyl 8-((3-((tert-butoxycarbonyl)amino)phenyl)amino)-8-oxooctanoate 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 7-(3-氨基苯基氨基甲酰基)庚酸甲酯
  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

• Light‐Controlled Histone Deacetylase (HDAC) Inhibitors: Towards Photopharmacological Chemotherapy
  作者：Wiktor Szymanski、Maria E. Ourailidou、Willem A. Velema、Frank J. Dekker、Ben L. Feringa

  DOI：10.1002/chem.201502809

  日期：2015.11.9

  In the case of chemotherapy, the systemic distribution of cytotoxic drugs reduces their efficacy and causes severe side effects due to nonselective toxicity. Photopharmacology allows a novel approach to address these problems because it employs external, local activation of chemotherapeutic agents by using light. The development of photoswitchable histone deacetylase (HDAC) inhibitors as potential antitumor

  癌症治疗存在局限性，这些局限性对患者的生活质量和生存产生重大影响。在化疗的情况下，细胞毒性药物的全身分布会降低其疗效并由于非选择性毒性而导致严重的副作用。光药理学允许一种新的方法来解决这些问题，因为它通过使用光利用外部、局部激活化学治疗剂。本文报道了作为潜在抗肿瘤剂的光开关组蛋白脱乙酰酶 (HDAC) 抑制剂的开发。临床上使用的化学治疗剂伏立诺他、帕比司他和贝立司他的类似物被设计成在其结构中加入了光可切换偶氮苯部分。最有希望的化合物在热力学不太稳定的环境中表现出高抑制效力就 HDAC 活性和 HeLa 细胞增殖而言，顺式形式和反式形式的活性显着降低。这种方法为 HDAC 抑制的局部光激活提供了明确的前景，以避免化疗中的严重副作用。
• Design and synthesis of potent dual inhibitors of JAK2 and HDAC based on fusing the pharmacophores of XL019 and vorinostat
  作者：Yu-yi Chu-Farseeva、Nurulhuda Mustafa、Anders Poulsen、Eng Chong Tan、Jeffrey J.Y. Yen、Wee Joo Chng、Brian W. Dymock

  DOI：10.1016/j.ejmech.2018.09.024

  日期：2018.10

  potencies against a panel of 4 solid tumor cell lines and 4 hematological cell lines with the most potent compound, 45h, having a cellular IC50 of 70 nM against the multiple myeloma cell line KMS-12-BM. Evidence of both JAK and HDAC pathway inhibition is presented in Hela cells showing that both pathways are modulated. Evidence of apoptosis with two compounds in 4 sold tumor cell lines is also presented

  大多数癌症治疗的主要手段是同时用多种不同的药物同时阻断癌细胞中一种以上的致癌途径。能够通过两种靶向途径做到这一点，而不会通过一般机制（例如化学疗法）引起副作用，这可能会给患者带来好处。在这项工作中，我们通过设计和开发基于JAK2选择性抑制剂XL019和泛HDAC抑制剂vorinostat的两种类型的分子，描述了JAK-STAT和HDAC途径的新型双重抑制剂。这两个系列的化合物均具有低纳摩尔分子JAK2和HDAC1 / 6抑制作用的实例。在某些情况下，在保持HDAC6活性的同时，实现了良好的HDAC1选择性。通过对所有三种酶的分子对接研究来解释观察到的效价。一个例子69c对其他三种JAK家族蛋白JAK1，JAK3和TYK2具有16-25倍的选择性。许多化合物对一组4种实体肿瘤细胞系和4种血液学细胞系具有亚微摩尔效价，其中最有效的化合物45h对多发性骨髓瘤细胞系KMS-12-BM的细胞IC 50为70
• 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.
• N-alkyl-hydroxybenzoyl anilide hydroxamates as dual inhibitors of HDAC and HSP90, downregulating IFN-γ induced PD-L1 expression
  作者：Samir Mehndiratta、Mei-Hsiang Lin、Yi-Wen Wu、Chun-Han Chen、Tung-Yun Wu、Kuo-Hsiang Chuang、Min-Wu Chao、Yi-Ying Chen、Shiow-Lin Pan、Mei-Chuan Chen、Jing-Ping Liou

  DOI：10.1016/j.ejmech.2019.111725

  日期：2020.1

  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.
• Synthesis and Biological Evaluation of Triazol-4-ylphenyl-Bearing Histone Deacetylase Inhibitors as Anticancer Agents
  作者：Rong He、Yufeng Chen、Yihua Chen、Andrei V. Ougolkov、Jin-San Zhang、Doris N. Savoy、Daniel D. Billadeau、Alan P. Kozikowski

  DOI：10.1021/jm901667k

  日期：2010.2.11

  Our triazole-based histone deacetylase inhibitor (HDACI), octanedioic acid hydroxyamide[3-(1-phenyl-1H-[1,2,3]triazol-4-yl)phenyl]amide (4a), suppresses pancreatic cancer cell growth in vitro with the lowest IC50 value of 20 nM against MiaPaca-2 cell. In this study, we continued our efforts to develop triazol-4-ylphenyl bearing hydroxamate analogues by embellishing the terminal phenyl ring of 4a with different substituents. The isoform inhibitory profile of these hydroxamate analogues was similar to those of 4a. All of these triazol-4-ylphenyl bearing hydroxamates are pan-HDACIs like SAHA. Moreover, compounds 4h and 11a were found to be very effective inhibitors of cancer cell growth in the HupT3 (IC50 = 50 nM) and MiaPaca-2 (IC50 = 40 nM) cancer cell lines, respectively. Compound 4a was found to reactivate the expression of CDK inhibitor proteins and to suppress pancreatic cancer cell growth in vivo. Taken together, these data further support the value of the triazol-4-ylphenyl bearing hydroxamates in identifying potential pancreatic cancer therapies.