(1R,2S,5S)-3-((S)-2-(3-(1-((叔丁基磺酰基)甲基)环己基)脲基)- | 1229337-32-9

• 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
• 中文名称: (1R,2S,5S)-3-((S)-2-(3-(1-((叔丁基磺酰基)甲基)环己基)脲基)-
• 英文名称: (1R,2S,5S)-3-((S)-2-(3-(1-(tert-butylsulfonylmethyl)cyclohexyl)ureido)-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylic acid
• 英文别名: (1R,2S,5S)-3-[(2S)-2-[[1-(tert-butylsulfonylmethyl)cyclohexyl]carbamoylamino]-3,3-dimethylbutanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylic acid
• CAS: 1229337-32-9
• 化学式: C₂₆H₄₅N₃O₆S
• 分子量: 527.726
• InChiKey: MNCDHDPDNUSTLV-CADBVGFASA-N

物化性质

• 沸点：
  751.2±45.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  141
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1R,2S,5S)-3-((S)-2-(3-(1-((叔丁基磺酰基)甲基)环己基)脲基)- 、 3-amino-N-ethyl-2-hydroxyheptanamide hydrochloride 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Discovery of Narlaprevir (SCH 900518): A Potent, Second Generation HCV NS3 Serine Protease Inhibitor

  摘要：

  Boceprevir (SCH 503034), 1, a novel HCV NS3 serine protease inhibitor discovered in our laboratories, is currently undergoing phase III clinical trials. Detailed investigations toward a second generation protease inhibitor culminated in the discovery of narlaprevir (SCH 900518), 37, with improved potency (similar to 10-fold over 1), pharmacokinetic profile and physicochemical characteristics, currently in phase II human trials. Exploration of synthetic sequence for preparation of 37 resulted in a route that required no silica gel purification for the entire synthesis.

  DOI：

  10.1021/ml9000276
• 作为产物：
  描述：

  环己甲酸甲酯 在 zinc dibromide N-甲基吗啉 、 Oxone 、 正丁基锂 、 叠氮磷酸二苯酯 、 水 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 二异丙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 2-甲基四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 甲苯 、 乙腈 为溶剂， -10.0~80.0 ℃ 、101.33 kPa 条件下， 反应 71.67h， 生成 (1R,2S,5S)-3-((S)-2-(3-(1-((叔丁基磺酰基)甲基)环己基)脲基)-
  参考文献：
  名称：

  [EN] ENANTIO- AND STEREO-SPECIFIC SYNTHESES OF ß-AMINO-a- HYDROXY AMIDES
  [FR] SYNTHÈSES ÉNANTIO- ET STÉRÉOSPÉCIFIQUES DE ?-AMINO-?-HYDROXYAMIDES

  摘要：

  用于制备化合物I的有用过程：公式（I）。用于制备化合物I的中间体，以及用于制备这些中间体的过程被披露。

  公开号：

  WO2011014494A1

文献信息

• Potent ketoamide inhibitors of HCV NS3 protease derived from quaternized P1 groups
  作者：Srikanth Venkatraman、Francisco Velazquez、Wanli Wu、Melissa Blackman、Vincent Madison、F. George Njoroge

  DOI：10.1016/j.bmcl.2010.02.051

  日期：2010.4

  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.
• ENANTIO- AND STEREO-SPECIFIC SYNTHESES OF -AMINO- - HYDROXY AMIDES
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2459525B1

  公开（公告）日：2017-03-01
• DEUTERATED COMPOUNDS AS HEPATITIS C VIRUS (HCV) INHIBITORS
  申请人：MacCoss Malcolm

  公开号：US20110286969A1

  公开（公告）日：2011-11-24

  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 wet! as methods of using them to treat disorders associated with the HCV protease An illustrative inventsve compound is shown below: Formula (I).
• ENANTIO- AND STEREO-SPECIFIC SYNTHESES OF BETA-AMINO-ALPHA- HYDROXY AMIDES
  申请人：Traverse John

  公开号：US20120178942A1

  公开（公告）日：2012-07-12

  Processes useful for the preparation of a Compound of Formula I: Formula (I). Intermediates useful for the preparation of the compound of Formula I, and processes useful for preparing said intermediates are disclosed.
• US8680294B2
  申请人：——

  公开号：US8680294B2

  公开（公告）日：2014-03-25