methyl-1N-(4-methoxyphenylsulfonyl)-4-oxo-pyrrolidine-(2R)-carboxylate | 203934-42-3

• 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-methoxyphenylsulfonyl)-4-oxo-pyrrolidine-(2R)-carboxylate
• 英文别名: methyl (2R)-1-(4-methoxyphenyl)sulfonyl-4-oxopyrrolidine-2-carboxylate
• CAS: 203934-42-3
• 化学式: C₁₃H₁₅NO₆S
• 分子量: 313.331
• InChiKey: QUVGYRMBTNSUDL-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  98.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl-1N-(4-methoxyphenylsulfonyl)-4-oxo-pyrrolidine-(2R)-carboxylate 在 氢氧化钾 、 羟胺 作用下， 以 甲醇 为溶剂， 生成 N-hydroxy 1N-(4-methoxyphenyl)sulfonyl-4-(Z,E-N-hydroxyimino)pyrrolidine-(2R)-carboxamide
  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：

  顺式-4-羟基-D-脯氨酸 在 4-二甲氨基吡啶 、 氯化亚砜 、 jones reagent 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 、 丙酮 为溶剂， 反应 42.0h， 生成 methyl-1N-(4-methoxyphenylsulfonyl)-4-oxo-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

• SPIROCYCLIC METALLOPROTEASE INHIBITORS
  申请人：THE PROCTER & GAMBLE COMPANY

  公开号：EP0927183B1

  公开（公告）日：2004-07-28
• US6015912A
  申请人：——

  公开号：US6015912A

  公开（公告）日：2000-01-18
• 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.