ethyl (1R,2S)-2-ethenyl-1-[[(2S,4S)-4-hydroxypyrrolidine-2-carbonyl]amino]cyclopropane-1-carboxylate | 1006654-83-6

• 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: ethyl (1R,2S)-2-ethenyl-1-[[(2S,4S)-4-hydroxypyrrolidine-2-carbonyl]amino]cyclopropane-1-carboxylate
• CAS: 1006654-83-6
• 化学式: C₁₃H₂₀N₂O₄
• 分子量: 268.313
• InChiKey: AKRMAAWQCISHQE-KEPMVKOISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl (1R,2S)-2-ethenyl-1-[[(2S,4S)-4-hydroxypyrrolidine-2-carbonyl]amino]cyclopropane-1-carboxylate 在 詹氏催化剂 、 偶氮二甲酸二异丙酯 、 N,N-二异丙基乙胺 、 三苯基膦 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 61.0h， 生成
  参考文献：
  名称：

  Discovery of Novel Urea-Based Hepatitis C Protease Inhibitors with High Potency against Protease-Inhibitor-Resistant Mutants

  摘要：

  The macrocyclic urea 2, a byproduct in the synthesis of benzoxaborole 1, was identified to be a novel and potent HCV protease inhibitor. We further explored this motif by synthesizing additional urea-based inhibitors and by characterizing them in replicase HCV protease-resistant mutants assay. Several compounds, exemplified by 12, were found to be more potent in HCV replicon assays than leading second generation inhibitors such as danoprevir and TMC-435350. Additionally, following oral administration, inhibitor 12 was found in rat liver in significantly higher concentrations than those reported for both danoprevir and TMC-435350, suggesting that inhibitor 12 has the combination of anti-HCV and pharmacokinetic properties that warrants further development of this series.

  DOI：

  10.1021/jm201278q
• 作为产物：
  描述：

  N-Boc-顺式-4-羟基-L-脯氨酸 在 盐酸 、 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 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 7.0h， 生成 ethyl (1R,2S)-2-ethenyl-1-[[(2S,4S)-4-hydroxypyrrolidine-2-carbonyl]amino]cyclopropane-1-carboxylate
  参考文献：
  名称：

  Discovery of Novel Urea-Based Hepatitis C Protease Inhibitors with High Potency against Protease-Inhibitor-Resistant Mutants

  摘要：

  The macrocyclic urea 2, a byproduct in the synthesis of benzoxaborole 1, was identified to be a novel and potent HCV protease inhibitor. We further explored this motif by synthesizing additional urea-based inhibitors and by characterizing them in replicase HCV protease-resistant mutants assay. Several compounds, exemplified by 12, were found to be more potent in HCV replicon assays than leading second generation inhibitors such as danoprevir and TMC-435350. Additionally, following oral administration, inhibitor 12 was found in rat liver in significantly higher concentrations than those reported for both danoprevir and TMC-435350, suggesting that inhibitor 12 has the combination of anti-HCV and pharmacokinetic properties that warrants further development of this series.

  DOI：

  10.1021/jm201278q

文献信息

• Phosphorus-containing hepatitis C serine protease inhibitors
  申请人：Moore Joel D.

  公开号：US20080039375A1

  公开（公告）日：2008-02-14

  The present invention relates to phosphorus-derived compounds of Formula I or Formula II, 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或式II的磷衍生化合物，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，尤其是丙型肝炎病毒（HCV）NS3-NS4A蛋白酶的活性。因此，本发明的化合物干扰丙型肝炎病毒的生命周期，并且还用作抗病毒剂。本发明进一步涉及包含上述化合物的药物组合物，用于给患有HCV感染的主体进行管理。本发明还涉及通过管理包含本发明化合物的药物组合物来治疗主体中的HCV感染的方法。
• N-FUNCTIONALIZED AMIDES AS HEPATITIS C SERINE PROTEASE INHIBITORS
  申请人：Niu Deqiang

  公开号：US20080267917A1

  公开（公告）日：2008-10-30

  The present invention relates to functionalized amides of Formula I or Formula II, including 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.

  本发明涉及式I或式II的功能化酰胺，包括抑制丝氨酸蛋白酶活性的药用可接受盐、酯或前药，尤其是丙型肝炎病毒（HCV）NS3-NS4A蛋白酶的活性。因此，本发明的化合物干扰丙型肝炎病毒的生命周期，并且也用作抗病毒剂。本发明进一步涉及包含上述化合物的药物组合物，用于给患有HCV感染的对象进行给药。本发明还涉及通过管理包含本发明化合物的药物组合物来治疗对象中的HCV感染的方法。
• MACROCYCLIC, PYRIDAZINONE-CONTAINING HEPATITIS C SERINE PROTEASE INHIBITORS
  申请人：Moore Joel D.

  公开号：US20090123425A1

  公开（公告）日：2009-05-14

  The present invention relates to compounds of Formula I, II, or III, 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 a compound of the present invention.

  本发明涉及公式I、II或III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，尤其是丙型肝炎病毒（HCV）NS3-NS4A蛋白酶的活性。因此，本发明的化合物干扰丙型肝炎病毒的生命周期，并且也用作抗病毒剂。本发明进一步涉及包含用于给予受HCV感染的主体的前述化合物的药物组合物。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主体中的HCV感染的方法。
• HYDRAZIDE-CONTAINING HEPATITIS C SERINE PROTEASE INHIBITORS
  申请人：MOORE JOEL D.

  公开号：US20080269228A1

  公开（公告）日：2008-10-30

  The present invention relates to novel hydrazide-containing compounds of Formula I or Formula II, including 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.

  本发明涉及式I或式II的新型含酰肼化合物，包括抑制丝氨酸蛋白酶活性的药物可接受的盐、酯或前药，尤其是丙型肝炎病毒（HCV）NS3-NS4A蛋白酶的活性。因此，本发明的化合物干扰丙型肝炎病毒的生命周期，并且还作为抗病毒剂是有用的。本发明进一步涉及包含上述化合物的药物组合物，用于给患有HCV感染的对象进行给药。本发明还涉及通过管理包含本发明化合物的药物组合物来治疗对象中的HCV感染的方法。
• [EN] MACROCYCLIC INHIBITORS OF HEPATITIS C PROTEASE<br/>[FR] INHIBITEURS MACROCYCLIQUES DE LA PROTÉASE DU VIRUS DE L'HÉPATITE C
  申请人：PHENOMIX CORP

  公开号：WO2010033466A1

  公开（公告）日：2010-03-25

  The invention provides macrocyclic compounds inhibitory to the Hepatitis C viral protease, compositions and combinations including the compounds, methods of treatment of conditions wherein inhibition of the Hepatitis C viral protease is medically indicated, and methods of treatment of a Hepatitis C viral infection in a human patient.

  本发明提供了一种抑制丙型肝炎病毒蛋白酶的大环化合物，包括该化合物的组合物、组合物、治疗方法，在医学上有抑制丙型肝炎病毒蛋白酶的指征的条件下的治疗方法，以及治疗人类患者丙型肝炎病毒感染的方法。