(E)-(S)-5-[(S)-1-(2,4-Dimethoxy-benzyl)-2-oxo-piperidin-3-yl]-4-((S)-3-(4-fluoro-phenyl)-2-{(S)-3-methyl-2-[(5-methyl-isoxazole-3-carbonyl)-amino]-butyrylamino}-propionylamino)-pent-2-enoic acid ethyl ester | 1025945-48-5

• 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: (E)-(S)-5-[(S)-1-(2,4-Dimethoxy-benzyl)-2-oxo-piperidin-3-yl]-4-((S)-3-(4-fluoro-phenyl)-2-{(S)-3-methyl-2-[(5-methyl-isoxazole-3-carbonyl)-amino]-butyrylamino}-propionylamino)-pent-2-enoic acid ethyl ester
• 英文别名: ethyl (E,4S)-5-[(3S)-1-[(2,4-dimethoxyphenyl)methyl]-2-oxopiperidin-3-yl]-4-[[(2S)-3-(4-fluorophenyl)-2-[[(2S)-3-methyl-2-[(5-methyl-1,2-oxazole-3-carbonyl)amino]butanoyl]amino]propanoyl]amino]pent-2-enoate
• CAS: 1025945-48-5
• 化学式: C₄₀H₅₀FN₅O₉
• 分子量: 763.864
• InChiKey: XQRJISIHXAHMMZ-OARKMKSBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  55
• 可旋转键数：
  19
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  178
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (E)-(S)-5-[(S)-1-(2,4-Dimethoxy-benzyl)-2-oxo-piperidin-3-yl]-4-((S)-3-(4-fluoro-phenyl)-2-{(S)-3-methyl-2-[(5-methyl-isoxazole-3-carbonyl)-amino]-butyrylamino}-propionylamino)-pent-2-enoic acid ethyl ester 在 水 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 氯仿 为溶剂， 反应 9.0h， 生成 (E)-(S)-4-((S)-3-(4-Fluoro-phenyl)-2-{(S)-3-methyl-2-[(5-methyl-isoxazole-3-carbonyl)-amino]-butyrylamino}-propionylamino)-5-((S)-2-oxo-piperidin-3-yl)-pent-2-enoic acid ethyl ester
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 4. Incorporation of P₁ Lactam Moieties as l-Glutamine Replacements

  摘要：

  The structure-based design, chemical synthesis, and biological evaluation of various human rhinovirus (HRV) 3C protease (3CP) inhibitors which incorporate P-1 lactam moieties in lieu of an L-glutamine residue are described. These compounds are comprised of a tripeptidyl or peptidomimetic binding determinant and an ethyl propenoate Michael acceptor moiety which forms an irreversible covalent adduct with the active site cysteine residue of the 3C enzyme. The P-1-lactam-containing inhibitors display significantly increased 3CP inhibition activity along with improved antirhinoviral properties relative to corresponding L-glutamine-derived molecules. In addition, several lactam-containing compounds exhibit excellent selectivity for HRV 3CP over several other serine and cysteine proteases and are not appreciably degraded by a variety of biological agents. One of the most potent inhibitors (AG7088, mean antirhinoviral EC90 0.10 approximate to mu M, n = 46 serotypes) is shown to warrant additional preclinical development to explore its potential for use as an antirhinoviral agent.

  DOI：

  10.1021/jm9805384
• 作为产物：
  描述：

  (4S)-4-(2'-carboxyethyl)-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester 在 N-甲基吗啉 、 盐酸 、 sodium perborate 、 硼烷四氢呋喃络合物 、 草酰氯 、 pyridine-SO3 complex 、 sodium acetate 、 sodium hexamethyldisilazane 、 三甲基乙酰氯 、 sodium cyanoborohydride 、 对甲苯磺酸 、 二甲基亚砜 、 1-羟基苯并三唑一水物 、 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 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 lithium chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 68.75h， 生成 (E)-(S)-5-[(S)-1-(2,4-Dimethoxy-benzyl)-2-oxo-piperidin-3-yl]-4-((S)-3-(4-fluoro-phenyl)-2-{(S)-3-methyl-2-[(5-methyl-isoxazole-3-carbonyl)-amino]-butyrylamino}-propionylamino)-pent-2-enoic acid ethyl ester
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 4. Incorporation of P₁ Lactam Moieties as l-Glutamine Replacements

  摘要：

  The structure-based design, chemical synthesis, and biological evaluation of various human rhinovirus (HRV) 3C protease (3CP) inhibitors which incorporate P-1 lactam moieties in lieu of an L-glutamine residue are described. These compounds are comprised of a tripeptidyl or peptidomimetic binding determinant and an ethyl propenoate Michael acceptor moiety which forms an irreversible covalent adduct with the active site cysteine residue of the 3C enzyme. The P-1-lactam-containing inhibitors display significantly increased 3CP inhibition activity along with improved antirhinoviral properties relative to corresponding L-glutamine-derived molecules. In addition, several lactam-containing compounds exhibit excellent selectivity for HRV 3CP over several other serine and cysteine proteases and are not appreciably degraded by a variety of biological agents. One of the most potent inhibitors (AG7088, mean antirhinoviral EC90 0.10 approximate to mu M, n = 46 serotypes) is shown to warrant additional preclinical development to explore its potential for use as an antirhinoviral agent.

  DOI：

  10.1021/jm9805384