N2-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N-[(1S)-1-cyano-2-(4-cyano-2-fluorophenyl)ethyl]-L-valinamide | 1159489-45-8

• 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: N2-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N-[(1S)-1-cyano-2-(4-cyano-2-fluorophenyl)ethyl]-L-valinamide
• 英文别名: (2S)-2-[[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]amino]-N-[(1S)-1-cyano-2-(4-cyano-2-fluorophenyl)ethyl]-3-methylbutanamide
• CAS: 1159489-45-8
• 化学式: C₂₃H₂₁BrF₄N₄O
• 分子量: 525.344
• InChiKey: ZZSKMRKSODYVIU-JBACZVJFSA-N

物化性质

• 沸点：
  633.3±55.0 °C(predicted)
• 密度：
  1.44±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  88.7
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [4-(1-Carbamoylcyclopropyl)phenyl]boronic acid 、 N2-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N-[(1S)-1-cyano-2-(4-cyano-2-fluorophenyl)ethyl]-L-valinamide 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-[4'-((1S)-1-{[(1S)-1-({[(1S)-1-cyano-2-(4-cyano-2-fluorophenyl)ethyl]amino}carbonyl)-2-methylpropyl]amino}-2,2,2-trifluoroethyl)biphenyl-4-yl]cyclopropanecarboxylic acid amide
  参考文献：
  名称：

  Identification of potent and reversible cruzipain inhibitors for the treatment of Chagas disease

  摘要：

  Identification of potent and reversible cruzipain inhibitors for the treatment of Chagas disease is described. The identified inhibitors bearing an amino nitrile warhead in P1 exhibit low nanomolar in vitro potency against cruzipain. Further SAR in P2 portion led to the identification of compounds, such as 26, that have a unique selectivity profile against other cysteine proteases and offering new opportunities for safer treatment of Chagas disease. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.015
• 作为产物：
  描述：

  N-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-L-valine 、 4-[(2S)-(2-amino-2-cyanoethyl)]-3-fluorobenzonitrile 在 2,6-二甲基吡啶 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N2-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N-[(1S)-1-cyano-2-(4-cyano-2-fluorophenyl)ethyl]-L-valinamide
  参考文献：
  名称：

  Identification of potent and reversible cruzipain inhibitors for the treatment of Chagas disease

  摘要：

  Identification of potent and reversible cruzipain inhibitors for the treatment of Chagas disease is described. The identified inhibitors bearing an amino nitrile warhead in P1 exhibit low nanomolar in vitro potency against cruzipain. Further SAR in P2 portion led to the identification of compounds, such as 26, that have a unique selectivity profile against other cysteine proteases and offering new opportunities for safer treatment of Chagas disease. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.015

文献信息

• CYSTEINE PROTEASE INHIBITORS FOR THE TREATMENT OF PARASITIC DISEASES
  申请人：ISABEL Elise

  公开号：US20130244962A1

  公开（公告）日：2013-09-19

  Several parasites responsible for mammalian diseases are dependent on cysteine protease for various life-cycle functions. Inhibition or decreasing function of these proteases can be useful in the treatment and/or prevention of these parasitic diseases including; toxoplasmosis, malaria, African trypanosomiasis, Chagas disease, leishmaniasis, schistosomiasis, amebiasis, giardiasis, clonorchiasis, opisthorchiasis, paragonimiasis, fasciolopsiasis, lymphatic filariasis, onchocerciasis, dracunculiasis, ascariasis, trichuriasis, stronglyoidiasis, trichostrongyliasis, trichomoniasis or cestodiasis.

  许多导致哺乳动物疾病的寄生虫依赖于半胱氨酸蛋白酶进行各种生命周期功能。抑制或降低这些蛋白酶的功能可以在治疗和/或预防这些寄生虫病方面发挥作用，包括弓形虫病、疟疾、非洲锥虫病、恙虫病、利什曼病、血吸虫病、阿米巴病、贾第鞭毛虫病、华支睾吸虫病、华支睾吸虫病、肺吸虫病、广篇吸虫病、淋巴丝虫病、昆虫媒介的皮下丝虫病、龙线虫病、蛔虫病、鞭虫病、强蛔虫病、阴道毛滴虫病或绦虫病。
• Cysteine protease inhibitors for the treatment of parasitic diseases
  申请人：Isabel Elise

  公开号：US08642799B2

  公开（公告）日：2014-02-04

  Several parasites responsible for mammalian diseases are dependent on cysteine protease for various life-cycle functions. Inhibition or decreasing function of these proteases can be useful in the treatment and/or prevention of these parasitic diseases including; toxoplasmosis, malaria, African trypanosomiasis, Chagas disease, leishmaniasis, schistosomiasis, amebiasis, giardiasis, clonorchiasis, opisthorchiasis, paragonimiasis, fasciolopsiasis, lymphatic filariasis, onchocerciasis, dracunculiasis, ascariasis, trichuriasis, stronglyoidiasis, trichostrongyliasis, trichomoniasis or cestodiasis.

  一些导致哺乳动物疾病的寄生虫依赖半胱氨酸蛋白酶进行各种生命周期功能。抑制或降低这些蛋白酶的功能可以在治疗和/或预防这些寄生虫病，包括弓形虫病、疟疾、非洲锥虫病、恙虫病、利什曼病、血吸虫病、阿米巴病、贾第虫病、华支睾吸虫病、华支睾吸虫病、肺吸虫病、巨吸虫病、淋巴丝虫病、昆虫体内丝虫病、龙虫病、蛔虫病、鞭虫病、强蛔虫病、阴道滴虫病或绦虫病中有用。
• CYSTEINE PROTEASE INHIBITORS FOR THE TREATMENT OF PARASITIC DISEASE
  申请人：Isabel Elise

  公开号：US20100305056A1

  公开（公告）日：2010-12-02

  Several parasites responsible for mammalian diseases are dependent on cysteine protease for various life-cycle functions. Inhibition or decreasing function of these proteases can be useful in the treatment and/or prevention of these parasitic diseases including; toxoplasmosis, malaria, African trypanosomiasis, Chagas disease, leishmaniasis, schistosomiasis, amebiasis, giardiasis, clonorchiasis, opisthorchiasis, paragonimiasis, fasciolopsiasis, lymphatic filariasis, onchocerciasis, dracunculiasis, ascariasis, trichuriasis, strongyloidiasis, trichostrongyliasis, trichomoniasis or cestodiasis. Compounds of formula I of the invention are capable of treating and/or preventing the above-identified diseases:

  一些导致哺乳动物疾病的寄生虫依赖半胱氨酸蛋白酶进行不同的生命周期功能。抑制或减少这些蛋白酶的功能可以用于治疗和/或预防这些寄生虫病，包括弓形虫病、疟疾、非洲锥虫病、恙虫病、利什曼病、血吸虫病、阿米巴病、贾第鞭毛虫病、华支睾吸虫病、华支睾吸虫病、肺吸虫病、巨吸虫病、淋巴丝虫病、眼虫病、蛔虫病、鞭虫病、弓形虫病。本发明的I式化合物能够治疗和/或预防上述疾病。
• US8642799B2
  申请人：——

  公开号：US8642799B2

  公开（公告）日：2014-02-04