methyl 1N-(4-n-propyloxyphenyl)-sulfonyl-4-exomethylene-pyrrolidine-(2R)-carboxylate | 256488-02-5

• 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: methyl 1N-(4-n-propyloxyphenyl)-sulfonyl-4-exomethylene-pyrrolidine-(2R)-carboxylate
• 英文别名: methyl (2R)-4-methylidene-1-(4-propoxyphenyl)sulfonylpyrrolidine-2-carboxylate
• CAS: 256488-02-5
• 化学式: C₁₆H₂₁NO₅S
• 分子量: 339.412
• InChiKey: WCALQTVNTJHCEM-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  81.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 1N-(4-n-propyloxyphenyl)-sulfonyl-4-exomethylene-pyrrolidine-(2R)-carboxylate 在 羟胺 作用下， 以 甲醇 为溶剂， 以168 mg的产率得到(R)-4-Methylene-1-(4-propoxy-benzenesulfonyl)-pyrrolidine-2-carboxylic acid hydroxyamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Matrix Metalloproteinase Inhibitors Derived from a Modified Proline Scaffold

  摘要：

  The synthesis and structure-activity relationship (SAR) studies of a series of proline-based matrix metalloproteinase inhibitors are described. The data reveal a remarkable potency enhancement in those compounds that contain an sp(2) center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a functionalized oxime moiety or an exomethylene at C-4, and the potencies were typically <10 nM for MMP-3 and <100 nM for MMP-1. Comparisons were then made against compounds with similar functionality where the C-4 carbon was reduced to sp(3) hybridization and the effect was typically an order of magnitude loss in potency. A comparison of compounds 14 and 34 exemplifies this observation. An X-ray structure was obtained for a stromelysin-inhibitor complex which provided insights into the SAR and selectivity trends observed within the series. In vitro intestinal permeability data for many compounds was also accumulated.

  DOI：

  10.1021/jm9904699
• 作为产物：
  描述：

  methyl 1N-tert-butoxycarbonyl-4-exomethylene-pyrrolidine-(2R)-carboxylate 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 生成 methyl 1N-(4-n-propyloxyphenyl)-sulfonyl-4-exomethylene-pyrrolidine-(2R)-carboxylate
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Matrix Metalloproteinase Inhibitors Derived from a Modified Proline Scaffold

  摘要：

  The synthesis and structure-activity relationship (SAR) studies of a series of proline-based matrix metalloproteinase inhibitors are described. The data reveal a remarkable potency enhancement in those compounds that contain an sp(2) center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a functionalized oxime moiety or an exomethylene at C-4, and the potencies were typically <10 nM for MMP-3 and <100 nM for MMP-1. Comparisons were then made against compounds with similar functionality where the C-4 carbon was reduced to sp(3) hybridization and the effect was typically an order of magnitude loss in potency. A comparison of compounds 14 and 34 exemplifies this observation. An X-ray structure was obtained for a stromelysin-inhibitor complex which provided insights into the SAR and selectivity trends observed within the series. In vitro intestinal permeability data for many compounds was also accumulated.

  DOI：

  10.1021/jm9904699

文献信息

• Design, Synthesis, and Biological Evaluation of Matrix Metalloproteinase Inhibitors Derived from a Modified Proline Scaffold
  作者：Menyan Cheng、Biswanath De、Neil G. Almstead、Stanislaw Pikul、Martin E. Dowty、Charles R. Dietsch、C. Michelle Dunaway、Fei Gu、Lily C. Hsieh、Michael J. Janusz、Yetunde O. Taiwo、Michael G. Natchus、Tomas Hudlicky、Martin Mandel

  DOI：10.1021/jm9904699

  日期：1999.12.1

  The synthesis and structure-activity relationship (SAR) studies of a series of proline-based matrix metalloproteinase inhibitors are described. The data reveal a remarkable potency enhancement in those compounds that contain an sp(2) center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a functionalized oxime moiety or an exomethylene at C-4, and the potencies were typically <10 nM for MMP-3 and <100 nM for MMP-1. Comparisons were then made against compounds with similar functionality where the C-4 carbon was reduced to sp(3) hybridization and the effect was typically an order of magnitude loss in potency. A comparison of compounds 14 and 34 exemplifies this observation. An X-ray structure was obtained for a stromelysin-inhibitor complex which provided insights into the SAR and selectivity trends observed within the series. In vitro intestinal permeability data for many compounds was also accumulated.