(2S,4S)-1-[(2S)-2-{[(tert-butoxy)carbonyl]amino}-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxylic acid | 817183-33-8

• 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: (2S,4S)-1-[(2S)-2-{[(tert-butoxy)carbonyl]amino}-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxylic acid
• 英文别名: (2S,4S)-1-((S)-2-((tert-Butoxycarbonyl)amino)-3,3-dimethylbutanoyl)-4-hydroxypyrrolidine-2-carboxylic acid；(2S,4S)-1-[(2S)-3,3-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]-4-hydroxypyrrolidine-2-carboxylic acid
• CAS: 817183-33-8
• 化学式: C₁₆H₂₈N₂O₆
• 分子量: 344.408
• InChiKey: XYXBVELFAOEJDK-GARJFASQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1R,2S)-1-氨基-2-乙烯基-环丙羧酸乙酯盐酸盐(1:1) 、 (2S,4S)-1-[(2S)-2-{[(tert-butoxy)carbonyl]amino}-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxylic acid 在 N,N-二异丙基乙胺 、 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， 反应 5.0h， 以66%的产率得到ethyl (1R,2S)-1-[[(2S,4S)-1-[(2S)-3,3-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]-4-hydroxypyrrolidine-2-carbonyl]amino]-2-ethenylcyclopropane-1-carboxylate
  参考文献：
  名称：

  TRIAZOLYL ACYCLIC HEPATITIS C SERINE PROTEASE INHIBITORS

  摘要：

  本发明涉及以下式I或II的化合物，或其药用盐、酯或前药：这些化合物抑制丝氨酸蛋白酶活性，特别是乙型肝炎病毒（HCV）NS3-NS4A蛋白酶的活性。因此，本发明的化合物干扰乙型肝炎病毒的生命周期，同时也可作为抗病毒剂使用。本发明还涉及包含上述化合物的药物组合物，用于治疗HCV感染的患者。该发明还涉及通过向患者施用包含本发明化合物的药物组合物来治疗患者的HCV感染的方法。

  公开号：

  US20080038225A1
• 作为产物：
  描述：

  (2S,4S)-1-((S)-2-((叔丁氧基羰基)氨基)-3,3-二甲基丁酰基)-4-羟基吡咯烷-2-羧酸甲酯 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 以93%的产率得到(2S,4S)-1-[(2S)-2-{[(tert-butoxy)carbonyl]amino}-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  针对衣原体中 HtrA 丝氨酸蛋白酶的 P2 修饰脯氨酸类似物的设计、合成和生物学评价

  摘要：

  高温要求 A (HtrA) 丝氨酸蛋白酶已成为一类新的抗菌靶标，在蛋白质质量控​​制中至关重要，并参与多种细菌感染的发病机制。以前，我们证明衣原体中的 HtrA对于细菌存活、复制和毒力至关重要。在这里，我们报告了一系列新的脯氨酸 (P2) 修饰的沙眼衣原体HtrA (CtHtrA) 抑制剂，通过脯氨酸环扩展和 Cγ-取代开发。基于结构的药物优化过程以分子建模和抑制效力、选择性和细胞毒性的体外药理学评价为指导。化合物25相对于肽先导化合物1，第一代 4 取代脯氨酸类似物的抗 CtHtrA 效力和对人中性粒细胞弹性蛋白酶 (HNE) 的选择性分别提高了约 6 倍和 12 倍。基于该化合物，通过区域选择性叠氮化物-炔烃点击化学合成了含有1,2,3-三唑部分的第二代取代脯氨酸残基。化合物49在全细胞试验中显示出显着提高的抗衣原体活性，在最低测试剂量下将细菌感染后代减少到检测限以下。相对于1 ，化合物49导致抑制效力和选择性提高约

  DOI：

  10.1016/j.ejmech.2021.114064

文献信息

• Acylaminoheteroaryl hepatitis C virus protease inhibitors
  申请人：Niu Deqiang

  公开号：US20080039470A1

  公开（公告）日：2008-02-14

  The present invention discloses compounds of formulae I and II, or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

  本发明揭示了式I和II的化合物，或其药用可接受的盐、酯或前药：这些化合物抑制丝氨酸蛋白酶活性，特别是乙型肝炎病毒（HCV）NS3-NS4A蛋白酶的活性。因此，本发明的化合物干扰了乙型肝炎病毒的生命周期，并且也可用作抗病毒剂。本发明还涉及包含上述化合物的药物组合物，用于给患有HCV感染的受试者进行治疗。本发明还涉及通过给予包含本发明化合物的药物组合物来治疗受试者的HCV感染的方法。
• Quinoxalinyl tripeptide hepatitis C virus inhibitors
  申请人：Gai Yonghua

  公开号：US20080032936A1

  公开（公告）日：2008-02-07

  The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

  本发明涉及式I的化合物，或其药用可接受的盐、酯或前药，其抑制丝氨酸蛋白酶活性，特别是乙型肝炎病毒（HCV）NS3-NS4A蛋白酶的活性。因此，本发明的化合物干扰了乙型肝炎病毒的生命周期，同时也可用作抗病毒药物。本发明还涉及包含上述化合物的药物组合物，用于治疗患有HCV感染的受试者。该发明还涉及通过给受试者投与含本发明化合物的药物组合物来治疗HCV感染的方法。
• TRIAZOLYL ACYCLIC HEPATITIS C SERINE PROTEASE INHIBITORS
  申请人：Sun Ying

  公开号：US20080038225A1

  公开（公告）日：2008-02-14

  The present invention relates to compounds of Formula I or II, or pharmaceutically acceptable salts, esters or prodrugs thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering to the subject a pharmaceutical composition comprising a compound of the present invention.

  本发明涉及以下式I或II的化合物，或其药用盐、酯或前药：这些化合物抑制丝氨酸蛋白酶活性，特别是乙型肝炎病毒（HCV）NS3-NS4A蛋白酶的活性。因此，本发明的化合物干扰乙型肝炎病毒的生命周期，同时也可作为抗病毒剂使用。本发明还涉及包含上述化合物的药物组合物，用于治疗HCV感染的患者。该发明还涉及通过向患者施用包含本发明化合物的药物组合物来治疗患者的HCV感染的方法。
• ACYCLIC OXIMYL HEPATITIS C PROTEASE INHIBITORS
  申请人：Sun Ying

  公开号：US20080187516A1

  公开（公告）日：2008-08-07

  The present invention discloses compounds of formula I or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
• ARYLPIPERIDINYL AND ARYLPYRROLIDINYL TRIPEPTIDE HEPATITIS C SERINE PROTEASE INHIBITORS
  申请人：Niu Deqiang

  公开号：US20080317712A1

  公开（公告）日：2008-12-25

  The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.