3-(N,N-dimethylamino)benzohydroxamate | 112072-21-6

• 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: 3-(N,N-dimethylamino)benzohydroxamate
• 英文别名: 3-dimethylamino-benzohydroxamic acid；3-Dimethylamino-benzohydroxamsaeure；3-(dimethylamino)-N-hydroxybenzamide
• CAS: 112072-21-6
• 化学式: C₉H₁₂N₂O₂
• mdl: MFCD02710404
• 分子量: 180.206
• InChiKey: XWYCFRKQCGRJSB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  52.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 3-(N,N-dimethylamino)benzohydroxamate 在 甲醇 、 乙醚 作用下， 生成 3-methoxycarbamoyl-tri-N-methyl-anilinium; iodide
  参考文献：
  名称：

  Benoit; Funke, Bulletin de la Societe Chimique de France, 1958, p. 257

  摘要：

  DOI：
• 作为产物：
  描述：

  间二甲氨基苯甲酸 在 盐酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 3-(N,N-dimethylamino)benzohydroxamate
  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

• 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.
• Benoit; Funke, Bulletin de la Societe Chimique de France, 1958, p. 257
  作者：Benoit、Funke

  DOI：——

  日期：——