(R)-2-{(S)-3-Methyl-3-[4-(2-methyl-quinolin-4-ylmethoxy)-phenyl]-2-oxo-pyrrolidin-1-yl}-propionic acid methyl ester | 478911-64-7

• 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: (R)-2-{(S)-3-Methyl-3-[4-(2-methyl-quinolin-4-ylmethoxy)-phenyl]-2-oxo-pyrrolidin-1-yl}-propionic acid methyl ester
• CAS: 478911-64-7
• 化学式: C₂₆H₂₈N₂O₄
• 分子量: 432.519
• InChiKey: LTEGSNAMOARVCT-DWXRJYCRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.17
• 重原子数：
  32.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  68.73
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (R)-2-{(S)-3-Methyl-3-[4-(2-methyl-quinolin-4-ylmethoxy)-phenyl]-2-oxo-pyrrolidin-1-yl}-propionic acid methyl ester 在 氢氧化钾 、 羟胺 作用下， 以 甲醇 为溶剂， 反应 0.42h， 以90%的产率得到IK682
  参考文献：
  名称：

  Discovery of γ-Lactam Hydroxamic Acids as Selective Inhibitors of Tumor Necrosis Factor α Converting Enzyme:  Design, Synthesis, and Structure−Activity Relationships

  摘要：

  New gamma-lactam. TACE inhibitors were designed from known MMP inhibitors. A homology model of TACE was built and examined to identify the S1' site as the key area for TACE selectivity over MMPs. Rational exploration of the P1'-S1' interactions resulted in the discovery of the 3,5-disubstituted benzyl ether as a TACE-selective P1' group. Further optimization led to the discovery of IK682 as a selective and orally bioavailable TACE inhibitor.

  DOI：

  10.1021/jm0255670
• 作为产物：
  描述：

  4-苄氧基苯基乙酸甲酯 在 palladium dihydroxide 氢气 、 sodium hexamethyldisilazane 、 caesium carbonate 、 臭氧 、 溶剂黄146 、 sodium iodide 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 9.5h， 生成 (R)-2-{(S)-3-Methyl-3-[4-(2-methyl-quinolin-4-ylmethoxy)-phenyl]-2-oxo-pyrrolidin-1-yl}-propionic acid methyl ester
  参考文献：
  名称：

  Discovery of γ-Lactam Hydroxamic Acids as Selective Inhibitors of Tumor Necrosis Factor α Converting Enzyme:  Design, Synthesis, and Structure−Activity Relationships

  摘要：

  New gamma-lactam. TACE inhibitors were designed from known MMP inhibitors. A homology model of TACE was built and examined to identify the S1' site as the key area for TACE selectivity over MMPs. Rational exploration of the P1'-S1' interactions resulted in the discovery of the 3,5-disubstituted benzyl ether as a TACE-selective P1' group. Further optimization led to the discovery of IK682 as a selective and orally bioavailable TACE inhibitor.

  DOI：

  10.1021/jm0255670