1-benzyl-2-thiohydantoin | 90915-07-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-benzyl-2-thiohydantoin
• 英文别名: 4-Imidazolidinone, 1-(phenylmethyl)-2-thioxo-；1-benzyl-2-sulfanylideneimidazolidin-4-one
• CAS: 90915-07-4
• 化学式: C₁₀H₁₀N₂OS
• mdl: MFCD04034668
• 分子量: 206.268
• InChiKey: SALZXYUJJZVVFD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-benzyl-2-thiohydantoin 、 5-吲哚甲醛 在 哌啶 作用下， 以 乙醇 为溶剂， 以41%的产率得到(Z)-5-((1H-indol-5-yl)methylene)-1-benzyl-2-thioxoimidazolidin-4-one
  参考文献：
  名称：

  5-Arylidenethioxothiazolidinones as Inhibitors of Tyrosyl–DNA Phosphodiesterase I

  摘要：

  Tyrosyl-DNA phosphodiesterase I (Tdp1) is a cellular enzyme that repairs the irreversible topoisomerase I (Top1)-DNA complexes and confers chemotherapeutic resistance to Top1 inhibitors. Inhibiting Tdp1 provides an attractive approach to potentiating clinically used Top1 inhibitors. However, despite recent efforts in studying Tdp1 as a therapeutic target, its inhibition remains poorly understood and largely underexplored. We describe herein the discovery of arylidene thioxothiazolidinone as a scaffold for potent Tdp1 inhibitors based on an initial tyrphostin lead compound 8. Through structure-activity relationship (SAR) studies we demonstrated that arylidene thioxothiazolidinones inhibit Tdp1 and identified compound 50 as a submicromolar inhibitor of Tdp1 (IC50 = 0.87 mu M). Molecular modeling provided insight into key interactions essential for observed activities. Some derivatives were also active against endogenous Tdp1 in whole cell extracts. These findings contribute to advancing the understanding on Tdp1 inhibition.

  DOI：

  10.1021/jm3008773
• 作为产物：
  描述：

  硫氰酸铵 、 N-苄基甘氨酸乙酯 在 water ethanol 、 乙醚 作用下， 反应 4.0h， 以to afford 1-benzyl-2-thiohydantoin (24.72 g), m.p. 150°-152° C.的产率得到1-benzyl-2-thiohydantoin
  参考文献：
  名称：

  4H-Imidazol-4-ones and their pharmaceutical use

  摘要：

  本发明涉及一种具有组胺H.sub.2-拮抗活性的Mannich-furyl（thienyl、pyridyl或phenyl）烷基氨基咪唑啉酮。本发明的一种特定化合物是2-[2-(5-二甲氨基甲基呋喃-2-基甲硫基)-乙基氨基]-1-甲基咪唑啉-4-酮。

  公开号：

  US04567176A1

文献信息

• 4H-Imidazol-4-ones and their pharmaceutical use
  申请人：Smith Kline & French Laboratories Limited

  公开号：US04567176A1

  公开（公告）日：1986-01-28

  This invention relates to Mannich-furyl(thienyl, pyridyl or phenyl) alkylaminoimidazolinones which have histamine H.sub.2 -antagonist activity. A specific compound of this invention is 2-[2-(5-dimethylaminomethylfuran-2-ylmethylthio)-ethylamino]-1-methyl-imid azolin-4-one.

  这项发明涉及具有组胺H.sub.2-拮抗活性的Mannich-呋喃（噻吩、吡啶或苯基）烷基氨基咪唑啉酮。该发明的具体化合物是2-[2-(5-二甲氨基甲基呋喃-2-基甲硫基)-乙基氨基]-1-甲基-咪唑啉-4-酮。
• Imidazolinone derivatives as histamine H2-antagonists
  申请人：SMITH KLINE & FRENCH LABORATORIES LIMITED

  公开号：EP0132914A2

  公开（公告）日：1985-02-13

  Compounds of the formula (I): and their salts are histamine H2-antagonists, wherein: R, and R2 are hydrogen or various substituted alkyl groups; n is 1 to 6; Z is 2,5-furanyl, 2,5-thienyl, 2,4-pyridyl (wherein R1R2N(CH2)n is at position 4) or 1,3 or 1,4-phenylene; m is zero or one; Y is oxygen, sulphur or methylene; p is 2 to 4; R4 and R5 are hydrogen, optionally substituted alkyl or phenyl, and R3 is hydrogen or optionally substituted alkyl. Pharmaceutical compositions containing them are described as are processes for their preparation and intermediates therefor.

  式（I）化合物及其盐类是组胺 H2-拮抗剂，其中：R 和 R2 是氢或各种取代的烷基；n 是 1 至 6；Z 是 2，5-呋喃基、2，5-噻吩基、2，4-吡啶基（其中 R1R2N(CH2)n 位于第 4 位）或 1，3 或 1，4-亚苯基；m 是 0 或 1；Y 是氧、硫或亚甲基；p 是 2 至 4；R4 和 R5 是氢、任选取代的烷基或苯基，R3 是氢或任选取代的烷基。 描述了含有这些化合物的药物组合物及其制备工艺和中间体。
• US4567176A
  申请人：——

  公开号：US4567176A

  公开（公告）日：1986-01-28
• [EN] AMINOIMIDAZOLONE DERIVATIVES AS HISTAMINE H2-ANTAGONISTS
  申请人：——

  公开号：WO1984004304A1

  公开（公告）日：1984-11-08

  (EN) Compounds of the formula (I) and their salts are histamine H2-antagonists, wherein : R1 and R2 are hydrogen or various substituted alkyl groups; n is 1 to 6; Z is 2,5-furanyl, 2,5-thienyl, 2,4-pyridyl (wherein R1R2N(CH2)n is at position 4) or 1,3 or 1,4-phenylene; m is zero or one; Y is oxygen, sulphur or methylene; p is 2 to 4; R4 and R5 are hydrogen, optionally substituted alkyl or phenyl, and R3 is hydrogen or optionally substituted alkyl. Pharmaceutical compositions containing them are described as are processes for their preparation and intermediates therefor. (FR) Composés de la formule (I) et leurs sels utilisés comme antagonistes de l"histamine H2, dans laquelle R1 et R2 représentent l"hydrogène ou divers groupes alcoyles substitués; n est compris entre 1 et 6; Z représente 2,5-furanyle, 2,5-thiényle, 2,4-pyridyle (où R1R2N(CH2)n se trouve en position 4) ou 1,3 ou 1,4-phénylène; m vaut zéro ou un; Y représente l"oxygène, le soufre ou le méthylène; p est compris entre 2 et 4; R4 et R5 représentent l"hydrogène, un alkyle ou un phényle éventuellement substitué, et R3 représente l"hydrogène ou un alkyle éventuellement substitué. Des compositions pharmaceutiques les contenant sont décrites ainsi que le sont des procédés permettant leur préparation et celle de leurs intermédiaires.
• 5-Arylidenethioxothiazolidinones as Inhibitors of Tyrosyl–DNA Phosphodiesterase I
  作者：Venkata Ramana Sirivolu、Sanjeev Kumar V. Vernekar、Christophe Marchand、Alena Naumova、Adel Chergui、Amelie Renaud、Andrew G. Stephen、Feng Chen、Yuk Y. Sham、Yves Pommier、Zhengqiang Wang

  DOI：10.1021/jm3008773

  日期：2012.10.25

  Tyrosyl-DNA phosphodiesterase I (Tdp1) is a cellular enzyme that repairs the irreversible topoisomerase I (Top1)-DNA complexes and confers chemotherapeutic resistance to Top1 inhibitors. Inhibiting Tdp1 provides an attractive approach to potentiating clinically used Top1 inhibitors. However, despite recent efforts in studying Tdp1 as a therapeutic target, its inhibition remains poorly understood and largely underexplored. We describe herein the discovery of arylidene thioxothiazolidinone as a scaffold for potent Tdp1 inhibitors based on an initial tyrphostin lead compound 8. Through structure-activity relationship (SAR) studies we demonstrated that arylidene thioxothiazolidinones inhibit Tdp1 and identified compound 50 as a submicromolar inhibitor of Tdp1 (IC50 = 0.87 mu M). Molecular modeling provided insight into key interactions essential for observed activities. Some derivatives were also active against endogenous Tdp1 in whole cell extracts. These findings contribute to advancing the understanding on Tdp1 inhibition.