3-cyclohexyl-5,5-bis(4-methoxyphenyl)-2-thioxoimidazolidin-4-one | 1505453-08-6

• 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-cyclohexyl-5,5-bis(4-methoxyphenyl)-2-thioxoimidazolidin-4-one
• 英文别名: 3-Cyclohexyl-5,5-bis(4-methoxyphenyl)-2-thioxoimidazolidin-4-one；3-cyclohexyl-5,5-bis(4-methoxyphenyl)-2-sulfanylideneimidazolidin-4-one
• CAS: 1505453-08-6
• 化学式: C₂₃H₂₆N₂O₃S
• 分子量: 410.537
• InChiKey: LZAYYXZPOHASKW-UHFFFAOYSA-N

物化性质

• 沸点：
  536.7±60.0 °C(predicted)
• 密度：
  1.28±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  82.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-cyclohexyl-5,5-bis(4-methoxyphenyl)-2-thioxoimidazolidin-4-one 在 叔丁基过氧化氢 、 ammonium hydroxide 作用下， 以 甲醇 为溶剂， 以1.7 g的产率得到3-cyclohexyl-2-imino-5,5-bis(4-methoxyphenyl)-imidazolidin-4-one
  参考文献：
  名称：

  Evaluation of Aminohydantoins as a Novel Class of Antimalarial Agents

  摘要：

  Given the threat of drug resistance, there is an acute need for new classes of antimalarial agents that act via a unique mechanism of action relative to currently used drugs. We have identified a set of druglike compounds within the Tres Cantos Anti-Malarial Set (TCAMS) which likely act via inhibition of a Plasmodium aspartic protease. Structure-activity relationship analysis and optimization of these aminohydantoins demonstrate that these compounds are potent nanomolar inhibitors of the Plasmodium aspartic proteases PM-II and PM-IV and likely one or more other Plasmodium aspartic proteases. Incorporation of a bulky group, such as a cyclohexyl group, on the aminohydantion N-3 position gives enhanced antimalarial potency while reducing inhibition of human aspartic proteases such as BACE. We have identified compound 8p (CWHM-117) as a promising lead for optimization as an antimalarial drug with a low molecular weight, modest lipophilicity, oral bioavailability, and in vivo antimalarial activity in mice.

  DOI：

  10.1021/ml400412x
• 作为产物：
  描述：

  N-(cyclohexylcarbamothioyl)benzamide 在 potassium carbonate 、 potassium hydroxide 作用下， 以 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 4.17h， 生成 3-cyclohexyl-5,5-bis(4-methoxyphenyl)-2-thioxoimidazolidin-4-one
  参考文献：
  名称：

  Evaluation of Aminohydantoins as a Novel Class of Antimalarial Agents

  摘要：

  Given the threat of drug resistance, there is an acute need for new classes of antimalarial agents that act via a unique mechanism of action relative to currently used drugs. We have identified a set of druglike compounds within the Tres Cantos Anti-Malarial Set (TCAMS) which likely act via inhibition of a Plasmodium aspartic protease. Structure-activity relationship analysis and optimization of these aminohydantoins demonstrate that these compounds are potent nanomolar inhibitors of the Plasmodium aspartic proteases PM-II and PM-IV and likely one or more other Plasmodium aspartic proteases. Incorporation of a bulky group, such as a cyclohexyl group, on the aminohydantion N-3 position gives enhanced antimalarial potency while reducing inhibition of human aspartic proteases such as BACE. We have identified compound 8p (CWHM-117) as a promising lead for optimization as an antimalarial drug with a low molecular weight, modest lipophilicity, oral bioavailability, and in vivo antimalarial activity in mice.

  DOI：

  10.1021/ml400412x

文献信息

• COMPOSITIONS AND METHODS FOR THE TREATMENT OF MALARIA
  申请人：Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences

  公开号：US20140296532A1

  公开（公告）日：2014-10-02

  The present invention provides aminohydantoin anti-malarial agents. In some embodiments, these agents have the property of functions of targeting malarial aspartic proteases while at the same time having low activity against human BACE. Methods of employing such agents are also provided.

  本发明提供了氨基咪唑啉类抗疟疾药物。在某些实施例中，这些药物具有靶向疟疾天冬氨酸蛋白酶的功能特性，同时对人类β-淀粉样蛋白前体酶的活性较低。本发明还提供了使用这些药物的方法。
• Compositions and methods for the treatment of malaria
  申请人：Saint Louis University

  公开号：US09353089B2

  公开（公告）日：2016-05-31

  The present invention provides aminohydantoin anti-malarial agents. In some embodiments, these agents have the property of functions of targeting malarial aspartic proteases while at the same time having low activity against human BACE. Methods of employing such agents are also provided.

  本发明提供了氨基咪唑啉类抗疟疾药剂。在某些实施例中，这些药剂具有靶向疟疾天冬氨酸蛋白酶的作用特性，同时对人类BACE的活性较低。还提供了使用这些药剂的方法。
• [EN] COMPOSITIONS AND METHODS FOR THE TREATMENT OF MALARIA<br/>[FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT DE LA MALARIA
  申请人：UNIV SAINT LOUIS

  公开号：WO2014160775A8

  公开（公告）日：2014-11-27
• US9353089B2
  申请人：——

  公开号：US9353089B2

  公开（公告）日：2016-05-31
• Evaluation of Aminohydantoins as a Novel Class of Antimalarial Agents
  作者：Marvin J. Meyers、Micky D. Tortorella、Jing Xu、Limei Qin、Zhengxiang He、Xingfen Lang、Wentian Zeng、Wanwan Xu、Li Qin、Michael J. Prinsen、Francis M. Sverdrup、Christopher S. Eickhoff、David W. Griggs、Jonathan Oliva、Peter G. Ruminski、E. Jon Jacobsen、Mary A. Campbell、David C. Wood、Daniel E. Goldberg、Xiaorong Liu、Yongzhi Lu、Xin Lu、Zhengchao Tu、Xiaoyun Lu、Ke Ding、Xiaoping Chen

  DOI：10.1021/ml400412x

  日期：2014.1.9

  Given the threat of drug resistance, there is an acute need for new classes of antimalarial agents that act via a unique mechanism of action relative to currently used drugs. We have identified a set of druglike compounds within the Tres Cantos Anti-Malarial Set (TCAMS) which likely act via inhibition of a Plasmodium aspartic protease. Structure-activity relationship analysis and optimization of these aminohydantoins demonstrate that these compounds are potent nanomolar inhibitors of the Plasmodium aspartic proteases PM-II and PM-IV and likely one or more other Plasmodium aspartic proteases. Incorporation of a bulky group, such as a cyclohexyl group, on the aminohydantion N-3 position gives enhanced antimalarial potency while reducing inhibition of human aspartic proteases such as BACE. We have identified compound 8p (CWHM-117) as a promising lead for optimization as an antimalarial drug with a low molecular weight, modest lipophilicity, oral bioavailability, and in vivo antimalarial activity in mice.