methyl (2R)-2-[(3S)-3-(4-hydroxyphenyl)-3-methyl-2-oxo-1-pyrrolidinyl]propanoate | 478911-32-9

• 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: methyl (2R)-2-[(3S)-3-(4-hydroxyphenyl)-3-methyl-2-oxo-1-pyrrolidinyl]propanoate
• 英文别名: methyl (2R)-2-[(3S)-3-(4-hydroxyphenyl)-3-methyl-2-oxopyrrolidin-1-yl]propanoate
• CAS: 478911-32-9
• 化学式: C₁₅H₁₉NO₄
• 分子量: 277.32
• InChiKey: LEQSZFHFHUVIKR-BMIGLBTASA-N

物化性质

• 沸点：
  456.2±45.0 °C(predicted)
• 密度：
  1.208±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (2R)-2-[(3S)-3-(4-hydroxyphenyl)-3-methyl-2-oxo-1-pyrrolidinyl]propanoate 在 氢氧化钾 、 羟胺 、 caesium carbonate 、 sodium iodide 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 2.92h， 生成 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：

  methyl 2-(4-benzyloxyphenyl)propionate 在 palladium dihydroxide 氢气 、 sodium hexamethyldisilazane 、 臭氧 、 溶剂黄146 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 methyl (2R)-2-[(3S)-3-(4-hydroxyphenyl)-3-methyl-2-oxo-1-pyrrolidinyl]propanoate
  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

文献信息

• Discovery of γ-Lactam Hydroxamic Acids as Selective Inhibitors of Tumor Necrosis Factor α Converting Enzyme:  Design, Synthesis, and Structure−Activity Relationships
  作者：James J.-W. Duan、Lihua Chen、Zelda R. Wasserman、Zhonghui Lu、Rui-Qin Liu、Maryanne B. Covington、Mingxin Qian、Karl D. Hardman、Ronald L. Magolda、Robert C. Newton、David D. Christ、Ruth R. Wexler、Carl P. Decicco

  DOI：10.1021/jm0255670

  日期：2002.11.1

  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.