(1S,2S,4S,7R)-6-aza-3,3-dimethyl-8-oxa-7-phenyltricyclo<4.3.0.0>nonan-5-one | 219753-99-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (1S,2S,4S,7R)-6-aza-3,3-dimethyl-8-oxa-7-phenyltricyclo<4.3.0.0>nonan-5-one
• 英文别名: (1S,2R,4S,7R)-3,3-dimethyl-7-phenyl-8-oxa-6-azatricyclo[4.3.0.02,4]nonan-5-one
• CAS: 219753-99-8
• 化学式: C₁₅H₁₇NO₂
• 分子量: 243.305
• InChiKey: CYONLFXTSHSHCO-HKUMRIAESA-N

物化性质

• 沸点：
  397.9±31.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1S,2S,4S,7R)-6-aza-3,3-dimethyl-8-oxa-7-phenyltricyclo<4.3.0.0>nonan-5-one 在 palladium on activated charcoal N-甲基吗啉 、 盐酸 、 二氯乙酸 、 lithium hydroxide 、 lithium aluminium tetrahydride 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 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 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 85.0h， 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：

  (3R,7aS)-3-Phenyl-5-trimethylsilanyloxy-7,7a-dihydro-1H-pyrrolo[1,2-c]oxazole 在 双氧水 作用下， 以 四氢呋喃 、 乙酸乙酯 、 甲苯 为溶剂， 反应 0.33h， 生成 (1S,2S,4S,7R)-6-aza-3,3-dimethyl-8-oxa-7-phenyltricyclo<4.3.0.0>nonan-5-one
  参考文献：
  名称：

  Cyclopropanation Reactions of Pyroglutamic Acid-Derived Synthons with Akylidene Transfer Reagents

  摘要：

  The cyclopropanation of unsaturated lactams 1 and 3 derived from pyroglutamic acid with nucleophilic alkylidene transfer reagents is investigated. Good-to-modest yields of cyclopropanes were obtained with most sulfur ylides explored. Syn/anti selectivity was found to be dependent on the synthon as well as the sulfur ylide. This cyclopropanation methodology is used in the synthesis of arginine and glutamic acid analogues.

  DOI：

  10.1021/jo9816109

文献信息

• Peptides for the treatment of HCV infections
  申请人：Masse Craig

  公开号：US20090175824A1

  公开（公告）日：2009-07-09

  This invention relates to novel compounds that are peptides derivatives and pharmaceutically acceptable salts thereof. More specifically, this invention relates to novel peptides that are derivatives of boceprevir. This invention also provides compositions comprising one or more compounds of this invention and a carrier and the use of the disclosed compounds and compositions in methods of treating diseases and conditions that are beneficially treated by administering an HCV NS3/NS4A protease inhibitor, such as boceprevir.

  本发明涉及新型化合物，它们是肽衍生物及其药学上可接受的盐。更具体地说，本发明涉及一种新型的肽衍生物，它是博西普韦的衍生物。本发明还提供了包含本发明中一种或多种化合物和载体的组合物，以及揭示的化合物和组合物在治疗通过给予HCV NS3/NS4A蛋白酶抑制剂（如博西普韦）有益治疗的疾病和病症的方法中的用途。
• Design, Synthesis and Evaluation of Poly-<scp>l</scp>-Proline Type-II Peptide Mimics Based on the 3-Azabicyclo[3.1.0]hexane System
  作者：Rui Zhang、Jose S. Madalengoitia

  DOI：10.1021/jo981814p

  日期：1999.1.1
• WO2009067225A2
  申请人：——

  公开号：——

  公开（公告）日：——