methyl 3-tert-butoxycarbonylamino-4-cyclobutyl-2-hydroxybutyrate | 394735-21-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl 3-tert-butoxycarbonylamino-4-cyclobutyl-2-hydroxybutyrate
• 英文别名: Methyl 4-cyclobutyl-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate
• CAS: 394735-21-8
• 化学式: C₁₄H₂₅NO₅
• 分子量: 287.356
• InChiKey: IEBFXLJCIQGTLU-UHFFFAOYSA-N

物化性质

• 沸点：
  423.5±35.0 °C(Predicted)
• 密度：
  1.128±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-tert-butoxycarbonylamino-4-cyclobutyl-2-hydroxybutyrate 在 N-甲基吗啉 N-甲基吗啉 、 盐酸 、 二氯乙酸 、 lithium hydroxide 、 氯化铵 、 二甲基亚砜 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 3-羟基-1,2,3-苯并三嗪-4(3H)-酮 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 128.0h， 生成 博赛泼维
  参考文献：
  名称：

  Discovery of (1R,5S)-N-[3-Amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a Selective, Potent, Orally Bioavailable Hepatitis C Virus NS3 Protease Inhibitor:  A Potential Therapeutic Agent for the Treatment of Hepatitis C Infection

  摘要：

  Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-alpha or polyethylene glycol (PEG)-interferon-alpha alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been advanced to clinical trials in human beings for the treatment of hepatitis C viral infections is described. X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed.

  DOI：

  10.1021/jm060325b
• 作为产物：
  描述：

  N-[1-(环丁基甲基)-2-(甲氧基甲基氨基)-2-氧代乙基]-氨基甲酸1,1-二甲基乙基酯 在 盐酸 、 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 37.0h， 生成 methyl 3-tert-butoxycarbonylamino-4-cyclobutyl-2-hydroxybutyrate
  参考文献：
  名称：

  Discovery of (1R,5S)-N-[3-Amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a Selective, Potent, Orally Bioavailable Hepatitis C Virus NS3 Protease Inhibitor:  A Potential Therapeutic Agent for the Treatment of Hepatitis C Infection

  摘要：

  Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-alpha or polyethylene glycol (PEG)-interferon-alpha alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been advanced to clinical trials in human beings for the treatment of hepatitis C viral infections is described. X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed.

  DOI：

  10.1021/jm060325b

文献信息

• 3,4-(cyclopentyl)-fused proline compounds as inhibitors of hepatitis C virus NS3 serine protease
  申请人：Njoroge George F.

  公开号：US20050197301A1

  公开（公告）日：2005-09-08

  The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.

  本发明公开了具有HCV蛋白酶抑制活性的新化合物，以及制备这种化合物的方法。在另一实施方式中，本发明公开了包含这种化合物的药物组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。
• [EN] CYCLOBUTENEDIONE GROUPS-CONTAINING COMPOUNDS AS INHIBITORS OF HEPATITIS C VIRUS NS3 SERINE PROTEASE<br/>[FR] GROUPES CYCLOBUTENEDIONE CONTENANT DES COMPOSES SERVANT D'INHIBITEURS A LA SERINE PROTEASE NS3 DU VIRUS DE L'HEPATITE C
  申请人：SCHERING CORP

  公开号：WO2005085197A1

  公开（公告）日：2005-09-15

  The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.

  本发明公开了具有HCV蛋白酶抑制活性的新化合物，以及制备这种化合物的方法。在另一实施方式中，本发明公开了包含这种化合物的药物组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。
• Methods of treating hepatitis C virus
  申请人：Gupta K. Samir

  公开号：US20060276406A1

  公开（公告）日：2006-12-07

  Methods for preventing, ameliorating or treating one or more symptoms of Hepatitis C virus (HCV), modulating HCV protease activity and/or inhibiting cathepsin activity in a subject, wherein the methods comprise administering to a subject in need of such treatment a dosage formulation containing at least one compound of Formulae I-XXVI herein, wherein the dosage formulation is capable of maintaining an average Cmin plasma concentration of the compound at or above 10 ng/ml.

  预防、改善或治疗丙型肝炎病毒（HCV）的一个或多个症状的方法，调节受试者中的HCV蛋白酶活性和/或抑制半胱氨酸蛋白酶活性，其中所述方法包括向需要此类治疗的受试者施用含有本文中的至少一种I-XXVI式化合物的剂量配方，其中剂量配方能够维持化合物的平均Cmin血浆浓度在或高于10 ng/ml。
• (1R,2S,5S)-N-[(1S)-3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3-[(2S)-2-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide as inhibitor of hepatitis C virus NS3/NS4a serine protease
  申请人：Njoroge George F.

  公开号：US20050249702A1

  公开（公告）日：2005-11-10

  The present invention discloses the compound of Formula 3 as an inhibitor of HCV protease, as well as methods for preparing the compound. In another embodiment, the invention discloses pharmaceutical compositions comprising the compound as well as methods of using them to treat disorders associated with the HCV protease.

  本发明公开了化合物Formula 3作为HCV蛋白酶抑制剂，以及制备该化合物的方法。在另一实施例中，本发明公开了包含该化合物的药物组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。
• Methods for treating hepatitis C
  申请人：Albrecht K. Janice

  公开号：US20060276405A1

  公开（公告）日：2006-12-07

  Methods of treating hepatitis C are provided comprising using a therapeutically effective amount of at least one novel hepatitis C (“HCV”) protease inhibitor or, alternatively, at least one antiviral or immuno-modulating HCV agent, which is not an HCV protease inhibitor, for a first treatment period. Subsequently, a combination of the at least one novel hepatitis C (“HCV”) protease inhibitor and the at least one antiviral or immuno-modulating HCV agent are administered in a therapeutically effective amount for a second treatment period. The methods are provided for treating a wide variety of diseases, disorders and symptoms associated with hepatitis C virus by modulating the activity of HCV protease (for example HCV NS3/NS4a serine protease) in a subject.

  提供了治疗丙型肝炎的方法，包括使用至少一种新型丙型肝炎（“HCV”）蛋白酶抑制剂的治疗有效量，或者选择至少一种不是HCV蛋白酶抑制剂的抗病毒或免疫调节HCV药物，用于第一治疗期。随后，在第二治疗期内以治疗有效量给予至少一种新型丙型肝炎（“HCV”）蛋白酶抑制剂和至少一种抗病毒或免疫调节HCV药物的组合。这些方法用于通过调节受试者中HCV蛋白酶（例如HCV NS3/NS4a丝氨酸蛋白酶）的活性来治疗与丙型肝炎病毒相关的各种疾病、疾病和症状。