(S)-2-(5-chlorothiophen-2-yl)-N-(1-(2-fluoro-4-(prop-1-en-2-yl)phenyl)-2-oxopyrrolidin-3-yl)ethenesulfonamide | 553651-58-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (S)-2-(5-chlorothiophen-2-yl)-N-(1-(2-fluoro-4-(prop-1-en-2-yl)phenyl)-2-oxopyrrolidin-3-yl)ethenesulfonamide
• 英文别名: (E)-2-(5-chlorothiophen-2-yl)-N-[(3S)-1-(2-fluoro-4-prop-1-en-2-ylphenyl)-2-oxopyrrolidin-3-yl]ethenesulfonamide
• CAS: 553651-58-4
• 化学式: C₁₉H₁₈ClFN₂O₃S₂
• 分子量: 440.947
• InChiKey: NNZZXQHYOLMHKT-DZZUKKPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (3S)-1-(2-fluoro-4-isopropenylphenyl)-2-oxopyrrolidin-3-ylcarbamic acid tert-butyl ester 、 2-(5-chloro-thiophen-2-yl)-ethenesulfonyl chloride 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 生成 (S)-2-(5-chlorothiophen-2-yl)-N-(1-(2-fluoro-4-(prop-1-en-2-yl)phenyl)-2-oxopyrrolidin-3-yl)ethenesulfonamide
  参考文献：
  名称：

  Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with monoaryl P4 motifs

  摘要：

  Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa inhibitors, incorporating neutral and basic monoaryl P4 groups, ultimately producing potent inhibitors with effective levels of anticoagulant activity and extended oral pharmacokinetic profiles. However, time dependant inhibition of Cytochrome P450 3A4 was a particular issue with this series.

  DOI：

  10.1016/j.bmcl.2009.11.077

文献信息

• Pyrrolidine-2-ones as factor xa inhibitors
  申请人：Borthwick David Alan

  公开号：US20050059726A1

  公开（公告）日：2005-03-17

  The present invention relates to novel compounds and pharmaceutically acceptable derivatives thereof. The invention also relates to processes for the preparation of the compounds, pharmaceutical compositions containing the compounds, and to the use of compounds in medicine, particularly in the amelioration of a clinical condition for which a Factor Xa inhibitor is indicated.

  本发明涉及新型化合物及其药学上可接受的衍生物。本发明还涉及制备该化合物的过程、含有该化合物的药物组合物以及化合物在医学上的使用，尤其是在改善适应于Xa因子抑制剂的临床病症方面的使用。
• Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with monoaryl P4 motifs
  作者：Savvas Kleanthous、Alan D. Borthwick、David Brown、Cynthia L. Burns-Kurtis、Matthew Campbell、Laiq Chaudry、Chuen Chan、Marie-Olive Clarte、Máire A. Convery、John D. Harling、Eric Hortense、Wendy R. Irving、Stephanie Irvine、Anthony J. Pateman、Angela N. Patikis、Ivan L. Pinto、Derek R. Pollard、Theresa J. Roethka、Stefan Senger、Gita P. Shah、Gary J. Stelman、John R. Toomey、Nigel S. Watson、Robert I. West、Caroline Whittaker、Ping Zhou、Robert J. Young

  DOI：10.1016/j.bmcl.2009.11.077

  日期：2010.1

  Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa inhibitors, incorporating neutral and basic monoaryl P4 groups, ultimately producing potent inhibitors with effective levels of anticoagulant activity and extended oral pharmacokinetic profiles. However, time dependant inhibition of Cytochrome P450 3A4 was a particular issue with this series.