(2S,3S,4E)-3-hydroxy-5-phenyl-2-(2-propen-1-yl)-4-pentenoic acid | 1431285-87-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂醇
• 英文名称: (2S,3S,4E)-3-hydroxy-5-phenyl-2-(2-propen-1-yl)-4-pentenoic acid
• 英文别名: (E,2S,3S)-3-hydroxy-5-phenyl-2-prop-2-enylpent-4-enoic acid
• CAS: 1431285-87-8
• 化学式: C₁₄H₁₆O₃
• 分子量: 232.279
• InChiKey: IHMRCVLDJVEJSN-MZWKFTRPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,3S,4E)-3-hydroxy-5-phenyl-2-(2-propen-1-yl)-4-pentenoic acid 在 2,6-二甲基吡啶 、 [1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene][3-bromopyridine]2 benzylidene ruthenium dichloride 、 二苯基膦叠氮化物 、 potassium carbonate 、 1-羟基苯并三唑 、 苯硫酚 、 1-丙基磷酸酐 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 15.5h， 生成 4-{[3-chloro-5-cyclopropyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyridin-2-yl]carbonyl}-1-((1S,2S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-cyclopenten-1-yl)-2-piperazinone
  参考文献：
  名称：

  Hepatitis C Replication Inhibitors That Target the Viral NS4B Protein

  摘要：

  We describe the preclinical development and in vivo efficacy of a novel chemical series that inhibits hepatitis C virus replication via direct interaction with the viral nonstructural protein 4B (NS4B). Significant potency improvements were realized through isosteric modifications to our initial lead la. The temptation to improve antiviral activity while compromising physicochemical properties was tempered by the judicial use of ligand efficiency indices during lead optimization. In this manner, compound la was transformed into (+)-28a which possessed an improved antiviral profile with no increase in molecular weight and only a modest elevation in lipophilicity. Additionally, we employed a chimeric "humanized" mouse model of HCV infection to demonstrate for the first time that a small molecule with high in vitro affinity for NS4B can inhibit viral replication in vivo. This successful proof-of-concept study suggests that drugs targeting NS4B may represent a viable treatment option for curing HCV infection.

  DOI：

  10.1021/jm400125h
• 作为产物：
  描述：

  (4R)-3-(4-pentenoyl)-4-(phenylmethyl)-1,3-oxazolidin-2-one 在 三甲基氯硅烷 、 sodium hexafluoroantimonate 、 lithium hydroxide monohydrate 、 双氧水 、 三乙胺 、 magnesium chloride 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 反应 17.0h， 生成 (2S,3S,4E)-3-hydroxy-5-phenyl-2-(2-propen-1-yl)-4-pentenoic acid
  参考文献：
  名称：

  Hepatitis C Replication Inhibitors That Target the Viral NS4B Protein

  摘要：

  We describe the preclinical development and in vivo efficacy of a novel chemical series that inhibits hepatitis C virus replication via direct interaction with the viral nonstructural protein 4B (NS4B). Significant potency improvements were realized through isosteric modifications to our initial lead la. The temptation to improve antiviral activity while compromising physicochemical properties was tempered by the judicial use of ligand efficiency indices during lead optimization. In this manner, compound la was transformed into (+)-28a which possessed an improved antiviral profile with no increase in molecular weight and only a modest elevation in lipophilicity. Additionally, we employed a chimeric "humanized" mouse model of HCV infection to demonstrate for the first time that a small molecule with high in vitro affinity for NS4B can inhibit viral replication in vivo. This successful proof-of-concept study suggests that drugs targeting NS4B may represent a viable treatment option for curing HCV infection.

  DOI：

  10.1021/jm400125h