(E)-tert-butyl 6-(3,7-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)-6-(4-methoxy-3-(methoxycarbamoyl)-5-methylphenyl)hex-5-enoate | 945965-69-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: (E)-tert-butyl 6-(3,7-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)-6-(4-methoxy-3-(methoxycarbamoyl)-5-methylphenyl)hex-5-enoate
• 英文别名: tert-Butyl (E)-6-(3,7-dimethyl-2-oxo-1,3-benzoxazol-5-yl)-6-[4-methoxy-3-(methoxycarbamoyl)-5-methyl-phenyl]hex-5-enoate；tert-butyl (E)-6-(3,7-dimethyl-2-oxo-1,3-benzoxazol-5-yl)-6-[4-methoxy-3-(methoxycarbamoyl)-5-methylphenyl]hex-5-enoate
• CAS: 945965-69-5
• 化学式: C₂₉H₃₆N₂O₇
• 分子量: 524.614
• InChiKey: UFXGNPYICJHKOU-SRZZPIQSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (E)-tert-butyl 6-(3,7-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)-6-(4-methoxy-3-(methoxycarbamoyl)-5-methylphenyl)hex-5-enoate 在 二乙胺基三氟化硫 、 三氟甲磺酸三甲基硅酯 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (Z)-5-((E)-1-(3,7-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)-5-(3-methyl-1,2,4-oxadiazol-5-yl)pent-1-enyl)-N,2-dimethoxy-3-methylbenzimidoyl fluoride
  参考文献：
  名称：

  WO2008/119028

  摘要：

  公开号：
• 作为产物：
  描述：

  tert-butyl hex-5-ynoate 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 (E)-tert-butyl 6-(3,7-dimethyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)-6-(4-methoxy-3-(methoxycarbamoyl)-5-methylphenyl)hex-5-enoate
  参考文献：
  名称：

  Synthesis and Anti-HIV Activity of New Metabolically Stable Alkenyldiarylmethane Non-Nucleoside Reverse Transcriptase Inhibitors Incorporating N-Methoxy Imidoyl Halide and 1,2,4-Oxadiazole Systems

  摘要：

  The alkenyldiarylmethanes (ADAMs) are a unique class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) that are capable of inhibiting HIV-1 reverse transcriptase (RT) through an allosteric mechanism. However, the potential usefulness of the ADAMs is limited by the presence of metabolically labile methyl ester moieties that are hydrolyzed by nonspecific esterases present in blood plasma, resulting in the formation of the inactive carboxylic acid metabolites. Therefore, to discover metabolically stable ADAMs, the design and synthesis of a new class of ADAMs with N-methoxy imidoyl halide and 1,2,4-oxadiazole systems were attempted. The resulting new ADAM 6 displayed enhanced metabolic stability in rat plasma (t(1/2) = 61 h) along with the ability to inhibit HIV-1 reverse transcriptase and the cytopathic effect of HIV-1(RF) and HIV-1(IIIB) at submicromolar concentrations.

  DOI：

  10.1021/jm070236e

文献信息

• WO2008/119028
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and Anti-HIV Activity of New Metabolically Stable Alkenyldiarylmethane Non-Nucleoside Reverse Transcriptase Inhibitors Incorporating <i>N</i>-Methoxy Imidoyl Halide and 1,2,4-Oxadiazole Systems
  作者：Takeshi Sakamoto、Matthew D. Cullen、Tracy L. Hartman、Karen M. Watson、Robert W. Buckheit、Christophe Pannecouque、Erik De Clercq、Mark Cushman

  DOI：10.1021/jm070236e

  日期：2007.7.1

  The alkenyldiarylmethanes (ADAMs) are a unique class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) that are capable of inhibiting HIV-1 reverse transcriptase (RT) through an allosteric mechanism. However, the potential usefulness of the ADAMs is limited by the presence of metabolically labile methyl ester moieties that are hydrolyzed by nonspecific esterases present in blood plasma, resulting in the formation of the inactive carboxylic acid metabolites. Therefore, to discover metabolically stable ADAMs, the design and synthesis of a new class of ADAMs with N-methoxy imidoyl halide and 1,2,4-oxadiazole systems were attempted. The resulting new ADAM 6 displayed enhanced metabolic stability in rat plasma (t(1/2) = 61 h) along with the ability to inhibit HIV-1 reverse transcriptase and the cytopathic effect of HIV-1(RF) and HIV-1(IIIB) at submicromolar concentrations.