(R,E)-2-(5-bromothiophen-2-yl)-N-((1-(1-(pyridin-4-yl)piperidine-4-carbonyl)pyrrolidin-3-yl)methyl)ethenesulfonamide | 958864-40-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (R,E)-2-(5-bromothiophen-2-yl)-N-((1-(1-(pyridin-4-yl)piperidine-4-carbonyl)pyrrolidin-3-yl)methyl)ethenesulfonamide
• 英文别名: (E)-2-(5-bromothiophen-2-yl)-N-[[(3R)-1-(1-pyridin-4-ylpiperidine-4-carbonyl)pyrrolidin-3-yl]methyl]ethenesulfonamide
• CAS: 958864-40-9
• 化学式: C₂₂H₂₇BrN₄O₃S₂
• 分子量: 539.517
• InChiKey: YEBAGUYJYNTFNJ-AAKUMTKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (E)-2-(5-bromothiophen-2-yl)-ethenesulfonyl chloride 、 在 碳酸氢钠 作用下， 以 乙酸乙酯 为溶剂， 生成 (R,E)-2-(5-bromothiophen-2-yl)-N-((1-(1-(pyridin-4-yl)piperidine-4-carbonyl)pyrrolidin-3-yl)methyl)ethenesulfonamide
  参考文献：
  名称：

  Amino(methyl) pyrrolidines as novel scaffolds for factor Xa inhibitors

  摘要：

  The design and synthesis of a novel class of amino(methyl) pyrrolidine-based sulforiamides as potent and selective FXa inhibitors is reported. The amino(methyl) pyrrolidine scaffolds were designed based on the proposed bioisosterism to the piperazine core in known FXa inhibitors. The SAR study led to compound 15 as the most potent FXa inhibitor in this series, with an IC50 Of 5.5 nM and PT EC2x. of 1.7 mu M. The proposed binding models show that the pyrrolidine cores are in van der Waals contact with the enzyme surface, and the flexibility of amino(methyl) pyrrolidines allows the two nitrogen atoms to anchor both the PI and P4 groups to fit similarly in the S I and S4 pockets. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.063

文献信息

• Amino(methyl) pyrrolidines as novel scaffolds for factor Xa inhibitors
  作者：Yan Shi、Doree Sitkoff、Jing Zhang、Wei Han、Zilun Hu、Philip D. Stein、Ying Wang、Lawrence J. Kennedy、Stephen P. O’Connor、Saleem Ahmad、Eddie C.-K. Liu、Steve M. Seiler、Patrick Y.S. Lam、Jeffrey A. Robl、John E. Macor、Karnail S. Atwal、Robert Zahler

  DOI：10.1016/j.bmcl.2007.07.063

  日期：2007.11

  The design and synthesis of a novel class of amino(methyl) pyrrolidine-based sulforiamides as potent and selective FXa inhibitors is reported. The amino(methyl) pyrrolidine scaffolds were designed based on the proposed bioisosterism to the piperazine core in known FXa inhibitors. The SAR study led to compound 15 as the most potent FXa inhibitor in this series, with an IC50 Of 5.5 nM and PT EC2x. of 1.7 mu M. The proposed binding models show that the pyrrolidine cores are in van der Waals contact with the enzyme surface, and the flexibility of amino(methyl) pyrrolidines allows the two nitrogen atoms to anchor both the PI and P4 groups to fit similarly in the S I and S4 pockets. (c) 2007 Elsevier Ltd. All rights reserved.