methyl 4-(2-phenylacetamido)benzoate | 97728-11-5

• 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 4-(2-phenylacetamido)benzoate
• 英文别名: Methyl 4-[(phenylacetyl)amino]benzoate；methyl 4-[(2-phenylacetyl)amino]benzoate
• CAS: 97728-11-5
• 化学式: C₁₆H₁₅NO₃
• mdl: MFCD00187741
• 分子量: 269.3
• InChiKey: XDBYHWVNGBJPSG-UHFFFAOYSA-N

物化性质

• 熔点：
  140-144 °C
• 沸点：
  487.5±38.0 °C(Predicted)
• 密度：
  1.217±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  methyl 4-(2-phenylacetamido)benzoate 在 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-dimethyl-d₆-formamide 为溶剂， 反应 15.0h， 生成 N-(2-amino-4-fluorophenyl)-4-(2-phenylacetamido)benzamide
  参考文献：
  名称：

  [EN] HDAC3-SELECTIVE INHIBITORS
  [FR] INHIBITEURS SÉLECTIFS DE HDAC3

  摘要：

  本文披露了选择性HDAC抑制剂。在某些实施例中，这些化合物是选择性HDAC3抑制剂。这些化合物可用于治疗各种疾病，包括癌症，如乳腺癌、虚弱和肝脂肪变性。

  公开号：

  WO2018223122A1
• 作为产物：
  描述：

  对氨基苯甲酸 在 氯化亚砜 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 methyl 4-(2-phenylacetamido)benzoate
  参考文献：
  名称：

  [EN] HDAC3-SELECTIVE INHIBITORS
  [FR] INHIBITEURS SÉLECTIFS DE HDAC3

  摘要：

  本文披露了选择性HDAC抑制剂。在某些实施例中，这些化合物是选择性HDAC3抑制剂。这些化合物可用于治疗各种疾病，包括癌症，如乳腺癌、虚弱和肝脂肪变性。

  公开号：

  WO2018223122A1

文献信息

• Palladium Catalyzed Aminocarbonylation of Benzylic Ammonium Triflates with Nitroarenes: Synthesis of Phenylacetamides
  作者：Li‐Miao Yang、Shan‐Shan Li、You‐Ya Zhang、Jin‐Liang Lu、Jing‐Tong Deng、Ai‐Jun Ma、Xiang‐Zhi Zhang、Shu‐Yu Zhang、Jin‐Bao Peng

  DOI：10.1002/adsc.202001561

  日期：2021.4.13

  A palladium catalyzed reductive aminocarbonylation of benzylic ammonium triflates with nitroarenes for the synthesis of phenylacetamides was developed. Using Pd(acac)2/DPPF catalyst system, a range of different substituted phenylacetamides were prepared in moderate to good yields from benzylic ammonium triflates and nitroarenes through Csp3−N bond cleavage. A variety of alkyl, aryl, and halide substituents

  开发了钯催化的苄基三氟甲磺酸铵与硝基芳烃的还原性氨基羰基化反应，用于合成苯乙酰胺。使用Pd（acac）2 / DPPF催化剂体系，通过Csp 3 -N键裂解，从苄基三氟甲磺酸铵和硝基芳烃以中等到良好的产率制备了一系列不同的取代苯基乙酰胺。可以在两个底物上使用多种烷基，芳基和卤化物取代基，并且可以容许许多有用的官能团。
• Synthesis and Evaluation of 3-(Dihydroxyboryl)benzoic Acids as <scp>d</scp>,<scp>d</scp>-Carboxypeptidase R39 Inhibitors
  作者：Steven R. Inglis、Astrid Zervosen、Esther C. Y. Woon、Thomas Gerards、Nathalie Teller、Delphine S. Fischer、André Luxen、Christopher J. Schofield

  DOI：10.1021/jm9009718

  日期：2009.10.8

  PBPs are of interest because bacteria have evolved resistance to the β-lactam antibiotics. Boronic acids have been developed as inhibitors of the mechanistically related serine β-lactamases and serine proteases; however, they have not been explored extensively as PBP inhibitors. Here we report aromatic boronic acid inhibitors of the d,d-carboxypeptidase R39 from Actinomadura sp. strain. Analogues of

  青霉素结合蛋白（PBPs）催化细菌细胞壁生物合成中的步骤，并且是β-内酰胺抗生素的靶标。靶向PBP的非β-内酰胺类抗生素引起人们的关注，因为细菌已发展出对β-内酰胺类抗生素的耐药性。已经开发出硼酸作为与机械相关的丝氨酸β-内酰胺酶和丝氨酸蛋白酶的抑制剂。然而，它们尚未作为PBP抑制剂得到广泛研究。在这里，我们报道来自Actinomadura sp。的d，d-羧肽酶R39的芳香族硼酸抑制剂。拉紧。最初发现的抑制剂[3-（二羟基硼基）苯甲酸1，IC 50通过涉及频哪醇硼酸酯的路线制备400μM]，所述频哪醇通过两步程序脱保护，该程序涉及中间三氟硼酸盐的水解，以水解得到游离的硼酸。在间位而不是邻位含有酰胺取代基的3-（二羟基硼基）苯甲酸类似物是R39 PBP的强效抑制剂高17倍，并且对其他PBP表现出一定的活性。这些化合物可用于开发甚至更有效的具有广谱抗菌活性的基于硼酸的PBP抑制剂。
• Selective inhibition of histone deacetylase 3 by novel hydrazide based small molecules as therapeutic intervention for the treatment of cancer
  作者：Sravani Pulya、Tarun Patel、Milan Paul、Nilanjan Adhikari、Suvankar Banerjee、Ganesh Routholla、Swati Biswas、Tarun Jha、Balaram Ghosh

  DOI：10.1016/j.ejmech.2022.114470

  日期：2022.8

  A promising hydrazide based small molecule lead as a potent and selective histone deacetylase 3 (HDAC3) inhibitor has been developed from a small series of synthesized novel chemical entities. The lead compound (4e) displayed high HDAC3 inhibitory potency (IC50 = 15.41 nM) and a minimum of 18-fold selectivity over other HDAC isoforms. It also exhibited potent cytotoxicity against several cancer cell

  一种有前途的基于酰肼的小分子铅作为一种有效和选择性的组蛋白脱乙酰酶 3 (HDAC3) 抑制剂已经从一小部分合成的新型化学实体中开发出来。先导化合物 ( 4e)显示出高 HDAC3 抑制效力 (IC 50  = 15.41 nM) 和比其他 HDAC 同工型至少高 18 倍的选择性。它还对几种癌细胞系表现出有效的细胞毒性，而对测试的正常细胞系的毒性最小。化合物4e还在体外和体内增强了 H3K9、H4K12 和 H3K27 的乙酰化水平. 它还在 B16F10 和 4T1 细胞中诱导 G2/M 期的细胞周期停滞。它引起明显的细胞凋亡，上调肿瘤组织中caspase-3、caspase-7、细胞色素c的表达，下调BCL2的表达。此外，CD44、EGFR 和 Ki-67 的下调表明化合物4e在减少小鼠细胞增殖和转移方面的潜力。此外，当在 4T1-Luc 异种移植小鼠模型中用4e治疗时，观察到肿瘤体
• Targeting breast cancer stem cells by novel HDAC3-selective inhibitors
  作者：Hao-Yu Hsieh、Hsiao-Ching Chuang、Fang-Hsiu Shen、Kinjal Detroja、Ling-Wei Hsin、Ching-Shih Chen

  DOI：10.1016/j.ejmech.2017.08.069

  日期：2017.11

  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.
• Zn²⁺-Chelating Motif-Tethered Short-Chain Fatty Acids as a Novel Class of Histone Deacetylase Inhibitors
  作者：Qiang Lu、Ya-Ting Yang、Chang-Shi Chen、Melanie Davis、John C. Byrd、Mark R. Etherton、Asad Umar、Ching-Shih Chen

  DOI：10.1021/jm0303655

  日期：2004.1.1

  Among various classes of histone deacetylase (HDAC) inhibitors, short-chain fatty acids exhibit the least potency, with IC50 in the millimolar range. We rationalized that this weak potency was, in part, attributable to their inability to access the zinc cation in the HDAC active-site pocket, which is pivotal to the deacetylation catalysis. We thus explored the structural optimization of valproate, butyrate, phenylacetate, and phenylbutyrate by coupling them with Zn2+-chelating motifs (hydroxamic acid and o-phenylenediamine) through aromatic W-amino acid linkers. This strategy has led to a novel class of Zn2+ -chelating, motif-tethered, short-chain fatty acids that exhibited varying degrees of HDAC inhibitory potency. One hydroxamate-tethered phenylbutyrate compound, N-hydroxy-4-(4-phenylbutyrylamino)benzamide (HTPB), displayed nanomolar potency in inhibiting HDAC activity. Exposure of several cancer cell lines to HTPB at the submicromolar level showed reduced cell proliferation accompanied by histone hyperacetylation and elevated p21(WAF/CIPI) expression, which are hallmark features associated with intracellular HDAC inhibition.