4-ethynyl-N-{(3S)-1-[(1S)-1-methyl-2-(4-morpholinyl)-2-oxoethyl]-2-oxo-3-pyrrolidinyl}benzenesulfonamide | 935458-10-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-ethynyl-N-{(3S)-1-[(1S)-1-methyl-2-(4-morpholinyl)-2-oxoethyl]-2-oxo-3-pyrrolidinyl}benzenesulfonamide
• 英文别名: 4-ethynyl-N-[(3S)-1-[(2S)-1-morpholin-4-yl-1-oxopropan-2-yl]-2-oxopyrrolidin-3-yl]benzenesulfonamide
• CAS: 935458-10-9
• 化学式: C₁₉H₂₃N₃O₅S
• 分子量: 405.475
• InChiKey: YCABCCNWHIGMCE-YOEHRIQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-ethynyl-N-{(3S)-1-[(1S)-1-methyl-2-(4-morpholinyl)-2-oxoethyl]-2-oxo-3-pyrrolidinyl}benzenesulfonamide 在 t-hexylborane 、 1,3-二甲基-2-咪唑啉酮 、 copper dichloride 作用下， 以 四氢呋喃 为溶剂， 反应 22.0h， 以34%的产率得到4-[(E)-2-chloroethenyl]-N-[(3S)-1-[(2S)-1-(morpholin-4-yl)-1-oxopropan-2-yl]-2-oxopyrrolidin-3-yl]benzene-1-sulfonamide
  参考文献：
  名称：

  Factor Xa Inhibitors:  S1 Binding Interactions of a Series of N-{(3S)-1-[(1S)-1-Methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides

  摘要：

  Factor Xa inhibitory activities for a series of N-{(3S)-1-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides with different P1 groups are described. These data provide insight into binding interactions within the S1 primary specificity pocket; rationales are presented for the derived SAR on the basis of electronic interactions through crystal structures of fXa-ligand complexes and molecular modeling studies. A good correlation between in vitro anticoagulant activities with lipophilicity and the extent of human serum albumin binding is observed within this series of potent fXa inhibitors. Pharmacokinetic profiles in rat and dog, together with selectivity over other trypsin-like serine proteases, identified 1f as a candidate for further evaluation.

  DOI：

  10.1021/jm060870c
• 作为产物：
  描述：

  (2S)-2-((3S)-3-{[(benzyloxy)carbonyl]amino}-2-oxopyrrolidin-1-yl)propanoic acid 在 bis-triphenylphosphine-palladium(II) chloride 、 palladium on activated charcoal 、 copper(l) iodide 吡啶 、 四丁基氟化铵 、 氢气 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 42.5h， 生成 4-ethynyl-N-{(3S)-1-[(1S)-1-methyl-2-(4-morpholinyl)-2-oxoethyl]-2-oxo-3-pyrrolidinyl}benzenesulfonamide
  参考文献：
  名称：

  Factor Xa Inhibitors:  S1 Binding Interactions of a Series of N-{(3S)-1-[(1S)-1-Methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides

  摘要：

  Factor Xa inhibitory activities for a series of N-{(3S)-1-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides with different P1 groups are described. These data provide insight into binding interactions within the S1 primary specificity pocket; rationales are presented for the derived SAR on the basis of electronic interactions through crystal structures of fXa-ligand complexes and molecular modeling studies. A good correlation between in vitro anticoagulant activities with lipophilicity and the extent of human serum albumin binding is observed within this series of potent fXa inhibitors. Pharmacokinetic profiles in rat and dog, together with selectivity over other trypsin-like serine proteases, identified 1f as a candidate for further evaluation.

  DOI：

  10.1021/jm060870c