methyl (1R,2S,5S)-3-{(2S)-2-[(tert-butoxycarbonyl)amino]-2-cyclohexylacetyl}-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate | 394735-24-1

• 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: methyl (1R,2S,5S)-3-{(2S)-2-[(tert-butoxycarbonyl)amino]-2-cyclohexylacetyl}-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate
• 英文别名: methyl (1R,2S,5S)-3-[(2S)-2-cyclohexyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate
• CAS: 394735-24-1
• 化学式: C₂₂H₃₆N₂O₅
• 分子量: 408.538
• InChiKey: SDUHZIYTQGSIQI-QAETUUGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (1R,2S,5S)-3-{(2S)-2-[(tert-butoxycarbonyl)amino]-2-cyclohexylacetyl}-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 methyl (1R,2S,5S)-3-((S)-2-amino-2-cyclohexylacetyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate hydrochloride
  参考文献：
  名称：

  Potent ketoamide inhibitors of HCV NS3 protease derived from quaternized P1 groups

  摘要：

  Blood borne hepatitis C infections are the primary cause for liver cirrhosis and hepatocellular carcinoma. HCV NS3 protease, a pivotal enzyme in the replication cycle of HCV virus has been the primary target for development of new drug candidates. Boceprevir and telaprevir are two novel ketoamide derived inhibitors that are currently undergoing phase-III clinical trials. These inhibitors include ketoamide functionality as serine trap and have an acidic alpha-ketoamide center that undergoes epimerization under physiological conditions. Our initial attempts to arrest this epimerization by introducing quaternary amino acids at P-1 had resulted in significantly diminished activity. In this manuscript we describe alpha quaternized P-1 group that result in potent inhibitors in the enzyme assay and demonstrate cellular activity comparable to boceprevir. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.02.051
• 作为产物：
  描述：

  (3R,7aS)-3-phenyl-3,7a-dihydro-1H-pyrrolo[1,2-c]oxazol-5-one 在 palladium on activated charcoal 盐酸 、 lithium aluminium tetrahydride 、 正丁基锂 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 丙酮 、 甲苯 为溶剂， 反应 18.0h， 生成 methyl (1R,2S,5S)-3-{(2S)-2-[(tert-butoxycarbonyl)amino]-2-cyclohexylacetyl}-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate
  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

• [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。
• [EN] NOVEL KETOAMIDES WITH CYCLIC P4'S AS INHIBITORS OF NS3 SERINE PROTEASE OF HEPATITIS C VIRUS<br/>[FR] NOUVEAUX CETOAMIDES A P4 CYCLIQUES EN TANT QU'INHIBITEURS DE LA NS3 SERINE PROTEASE DU VIRUS DE L'HEPATITE C
  申请人：SCHERING CORP

  公开号：WO2005085242A1

  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，该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。
• Novel peptides as NS3-serine protease inhibitors of hepatitis C virus
  申请人：Njoroge George F.

  公开号：US20070232549A1

  公开（公告）日：2007-10-04

  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.

  本发明揭示了具有HCV蛋白酶抑制活性的新化合物，以及制备这些化合物的方法。在另一种实施方式中，本发明揭示了包含这些化合物的制药组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。
• NOVEL PEPTIDES AS NS3-SERINE PROTEASE INHIBITORS OF HEPATITIS C VIRUS
  申请人：Saksena Anil K.

  公开号：US20110117057A1

  公开（公告）日：2011-05-19

  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.

  本发明披露了具有HCV蛋白酶抑制活性的新化合物，以及制备这些化合物的方法。在另一种实施方式中，本发明披露了包含这些化合物的制药组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。
• Nitrile-containing antiviral compounds
  申请人：Pfizer Inc.

  公开号：US11351149B2

  公开（公告）日：2022-06-07

  The invention relates to compounds of Formula I″ wherein R, R1, R2, R3, p, q and q′ are as defined herein, pharmaceutical compositions comprising the compounds, methods of treating coronavirus infection such as COVID-19 in a patient by administering therapeutically effective amounts of the compounds, and methods of inhibiting or preventing replication of coronaviruses such as SARS-CoV-2 with the compounds.

  本发明涉及式 I″ 的化合物 其中R、R1、R2、R3、p、q和q′如本文所定义；包含该化合物的药物组合物；通过施用治疗有效量的该化合物治疗患者冠状病毒感染如COVID-19的方法；以及用该化合物抑制或防止冠状病毒如SARS-CoV-2复制的方法。