methyl 3-amino-4-ethoxybenzoate

• 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 3-amino-4-ethoxybenzoate
• 英文别名: 4-ethoxy-3-amino-benzoic acid methyl ester；4-Aethoxy-3-amino-benzoesaeure-methylester
• 化学式: C₁₀H₁₃NO₃
• 分子量: 195.218
• InChiKey: YZNOKVXAKUGUQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-amino-4-ethoxybenzoate 在 arsenic(V) oxide 、 硫酸 、 甘油 作用下， 生成 8-乙氧基-5-喹啉羧酸
  参考文献：
  名称：

  Moness; Christiansen, Journal of the American Pharmaceutical Association (1912), 1936, vol. 25, p. 501,503

  摘要：

  DOI：
• 作为产物：
  描述：

  对乙氧基苯甲酸 在 盐酸 、 氯化亚砜 、 硫酸 、 硝酸 、 铁粉 作用下， 以 甲醇 、 水 为溶剂， 反应 2.5h， 生成 methyl 3-amino-4-ethoxybenzoate
  参考文献：
  名称：

  Structure-Based Design and Synthesis of Novel Inhibitors Targeting HDAC8 from Schistosoma mansoni for the Treatment of Schistosomiasis

  摘要：

  Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. In this study, a series of new benzohydroxamates were prepared as potent inhibitors of Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into the: inhibition mode of smHDAC8 activity by these 3-amidobenzohydroxamates. The newly designed inhibitors were evaluated in screens for enzyme inhibitory activity against schistosome and human HDACs. Twenty-seven compounds were found to be active in the nanomolar range, and some of them showed selectivity toward smHDAC8 over the major human HDACs (I and 6). The active benzohydroxamates were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Four of these showed significant dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture.

  DOI：

  10.1021/acs.jmedchem.5b01478

文献信息

• Synthesis, structure-activity relationships, cocrystallization and cellular characterization of novel smHDAC8 inhibitors for the treatment of schistosomiasis
  作者：Ehab Ghazy、Tino Heimburg、Julien Lancelot、Patrik Zeyen、Karin Schmidtkunz、Anne Truhn、Salma Darwish、Conrad V. Simoben、Tajith B. Shaik、Frank Erdmann、Matthias Schmidt、Dina Robaa、Christophe Romier、Manfred Jung、Raymond Pierce、Wolfgang Sippl

  DOI：10.1016/j.ejmech.2021.113745

  日期：2021.12

  available drug, praziquantel. In this study, we chemically optimized our previously reported benzhydroxamate-based inhibitors of Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into the inhibition mode of smHDAC8 activity by the highly potent inhibitor 5o. Structure-based optimization of the novel inhibitors was carried out using the available crystal structures

  血吸虫病是一种被忽视的主要寄生虫病，影响全球超过 2.65 亿人，其控制策略包括使用唯一可用的药物吡喹酮进行大规模治疗。在这项研究中，我们对我们之前报道的基于苯甲羟肟酸盐的曼氏血吸虫组蛋白脱乙酰酶 8 (smHDAC8) 抑制剂进行了化学优化。晶体学分析提供了对高效抑制剂5o对 smHDAC8 活性的抑制模式的见解. 使用可用的晶体结构以及对 smHDAC8 的对接研究对新型抑制剂进行了基于结构的优化。在筛选中评估了这些化合物对血吸虫和人类 HDAC (hHDAC) 的抑制活性。体外和对接结果用于详细的结构活性关系。使用基于荧光的测定法进一步研究合成的化合物对血吸虫幼虫阶段的杀伤力。最有希望的抑制剂5o显示出显着的剂量依赖性杀死血吸虫幼虫和显着损害培养中的成虫对的产卵。
• 抗肿瘤药物来那替尼的中间体及其制备与应用
  申请人：中国科学院上海药物研究所

  公开号：CN102731395A

  公开（公告）日：2012-10-17

  本发明涉及一种如式I所示的来那替尼的中间体化合物或其酸加成盐、其制备方法和用于制备来那替尼的用途。在式I中，A为氢、离去基团或二甲基氨基；所述离去基团为卤素、甲磺酰氧基、三氟甲磺酰氧基或甲基苯磺酰氧基；所述中间体化合物的酸加成盐为：当A为二甲基氨基时，式I所示化合物的无机酸盐或有机酸盐。
• Synthetische Studien über die Beziehung zwischen chemischer Konstitution und antimikrober Wirkung XII. 3-Nitro- und 3-Amino-4-oxy bzw. alkoxybenzoesäureester
  作者：Th. Sabalitschka、K. H. Tiedge

  DOI：10.1002/ardp.19342721022

  日期：——
• Structure-Based Design and Synthesis of Novel Inhibitors Targeting HDAC8 from <i>Schistosoma mansoni</i> for the Treatment of Schistosomiasis
  作者：Tino Heimburg、Alokta Chakrabarti、Julien Lancelot、Martin Marek、Jelena Melesina、Alexander-Thomas Hauser、Tajith B. Shaik、Sylvie Duclaud、Dina Robaa、Frank Erdmann、Matthias Schmidt、Christophe Romier、Raymond J. Pierce、Manfred Jung、Wolfgang Sippl

  DOI：10.1021/acs.jmedchem.5b01478

  日期：2016.3.24

  Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. In this study, a series of new benzohydroxamates were prepared as potent inhibitors of Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into the: inhibition mode of smHDAC8 activity by these 3-amidobenzohydroxamates. The newly designed inhibitors were evaluated in screens for enzyme inhibitory activity against schistosome and human HDACs. Twenty-seven compounds were found to be active in the nanomolar range, and some of them showed selectivity toward smHDAC8 over the major human HDACs (I and 6). The active benzohydroxamates were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Four of these showed significant dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture.
• Moness; Christiansen, Journal of the American Pharmaceutical Association (1912), 1936, vol. 25, p. 501,503
  作者：Moness、Christiansen

  DOI：——

  日期：——