2-(2-carbamothioylhydrazono)butanoic acid | 89417-93-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-(2-carbamothioylhydrazono)butanoic acid
• 英文别名: 2-ketobutyric acid thiosemicarbazone；2-thiosemicarbazono-butyric acid；2-Thiosemicarbazono-buttersaeure；2-(Carbamothioylhydrazinylidene)butanoic acid
• CAS: 89417-93-6
• 化学式: C₅H₉N₃O₂S
• 分子量: 175.211
• InChiKey: QAUMLWNGJDDTGX-UHFFFAOYSA-N

物化性质

• 熔点：
  172-173 °C(Solv: water (7732-18-5))
• 沸点：
  342.5±25.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2-carbamothioylhydrazono)butanoic acid 在 sodium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 7.0h， 生成 6-ethyl-3-(methylthio)-1,2,4-triazin-5-ol
  参考文献：
  名称：

  Original 2-(3-Alkoxy-1H-pyrazol-1-yl)azines Inhibitors of Human Dihydroorotate Dehydrogenase (DHODH)

  摘要：

  Following our discovery of human dihydroorotate dehydrogenase (DHODH) inhibition by 2-(3-alkoxy-1H-pyrazol-1-yl)pyrimidine derivatives as well as 2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-methylpyridine, we describe here the syntheses and evaluation of an array of azine-bearing analogues. As in out previous report, the structure activity study of this series of human DHODH inhibitors was based on a phenotypic assay measuring measles virus replication. Among other inhibitors, this round of syntheses and biological evaluation iteration led to the highly active 5-cyclopropyl-2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-3-fluoropyridine. Inhibition of DHODH by this compound was confirmed in an array of in vitro assays, including enzymatic tests and cell-based assays for viral replication and cellular growth. This molecule was found to be more active than the known inhibitors of DHODH, brequinar and teriflunomide, thus opening perspectives for its Use as a tool or for the design of an original series of immunosuppressive agent. Moreover, because other Series of inhibitors of human DHODH have been found to also affect Plasmodium falciparum DHODH, all the compounds were assayed for their effect on P. falciparum growth. However, the modest in vitro inhibition solely observed for two compounds did not correlate with their inhibition of P. falciparum DHODH.

  DOI：

  10.1021/acs.jmedchem.5b00606
• 作为产物：
  描述：

  2-酮丁酸 、 氨基硫脲 在 水 作用下， 生成 2-(2-carbamothioylhydrazono)butanoic acid
  参考文献：
  名称：

  Gut; Prystas, Collection of Czechoslovak Chemical Communications, 1959, vol. 24, p. 2986,2988

  摘要：

  DOI：

文献信息

• Inequivalent coordination of thiosemicarbazone ligands in cobalt (III) and chromium (III) complexes
  作者：Pramila Sonawane、Rajeev Chikate、Avinash Kumbhar、Subhash Padhye、Robert J. Doedens

  DOI：10.1016/s0277-5387(00)81652-6

  日期：1994.1

  Chromium (III) and cobalt (III) complexes derived from 2-ketobutyric acid thiosemicarbazone (H2Kbtsc) have been prepared and characterized. Crystal structure analyses have shown both products to be mixed ligand complexes of the type M(HKbtsc) (Kbtsc) in which the thiosemicarbazone ligand is present in singly deprotonated “thione” and doubly deprotonated “thiol” forms. In each complex, the metal ion is

  制备并表征了衍生自2-酮丁酸硫代半碳H（H 2 Kbtsc）的铬（III）和钴（III）配合物。晶体结构分析表明，两种产物均为M（HKbtsc）（Kbtsc）型混合配体配合物，其中的硫半脲酮配体以单去质子化的“硫酮”和双去质子化的“硫醇”形式存在。在每个络合物中，金属离子通过子午立体化学以扭曲的八面体几何形状与两个三齿配体结合。观察到两种类型的配体之间的微小但一致的结构差异。光谱和电化学数据与从晶体学结果得出的这些化合物的配方一致。
• Gut; Prystas, Collection of Czechoslovak Chemical Communications, 1959, vol. 24, p. 2986,2988
  作者：Gut、Prystas

  DOI：——

  日期：——
• Libermann,D.; Jacquier,R., Bulletin de la Societe Chimique de France, 1961, p. 383 - 390
  作者：Libermann,D.、Jacquier,R.

  DOI：——

  日期：——
• Godfrin, Journal de Pharmacie et de Chimie, 1939, vol. <8> 30, p. 324,326
  作者：Godfrin

  DOI：——

  日期：——
• Original 2-(3-Alkoxy-1<i>H</i>-pyrazol-1-yl)azines Inhibitors of Human Dihydroorotate Dehydrogenase (DHODH)
  作者：Marianne Lucas-Hourani、Hélène Munier-Lehmann、Farah El Mazouni、Nicholas A. Malmquist、Jane Harpon、Eloi P. Coutant、Sandrine Guillou、Olivier Helynck、Anne Noel、Artur Scherf、Margaret A. Phillips、Frédéric Tangy、Pierre-Olivier Vidalain、Yves L. Janin

  DOI：10.1021/acs.jmedchem.5b00606

  日期：2015.7.23

  Following our discovery of human dihydroorotate dehydrogenase (DHODH) inhibition by 2-(3-alkoxy-1H-pyrazol-1-yl)pyrimidine derivatives as well as 2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-methylpyridine, we describe here the syntheses and evaluation of an array of azine-bearing analogues. As in out previous report, the structure activity study of this series of human DHODH inhibitors was based on a phenotypic assay measuring measles virus replication. Among other inhibitors, this round of syntheses and biological evaluation iteration led to the highly active 5-cyclopropyl-2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-3-fluoropyridine. Inhibition of DHODH by this compound was confirmed in an array of in vitro assays, including enzymatic tests and cell-based assays for viral replication and cellular growth. This molecule was found to be more active than the known inhibitors of DHODH, brequinar and teriflunomide, thus opening perspectives for its Use as a tool or for the design of an original series of immunosuppressive agent. Moreover, because other Series of inhibitors of human DHODH have been found to also affect Plasmodium falciparum DHODH, all the compounds were assayed for their effect on P. falciparum growth. However, the modest in vitro inhibition solely observed for two compounds did not correlate with their inhibition of P. falciparum DHODH.