3-chloro-N-[(3S)-1-(2-fluoro-4-pyrrolidin-2-ylphenyl)-2-oxopyrrolidin-3-yl]-1H-indole-6-sulfonamide | 1293979-54-0

• 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: 3-chloro-N-[(3S)-1-(2-fluoro-4-pyrrolidin-2-ylphenyl)-2-oxopyrrolidin-3-yl]-1H-indole-6-sulfonamide
• CAS: 1293979-54-0
• 化学式: C₂₂H₂₂ClFN₄O₃S
• 分子量: 476.959
• InChiKey: ZNPDOYMGSIHJPU-GGYWPGCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  103
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 吡啶 、 20 % Pd(OH)2/C 、 四丁基氟化铵 、 氢气 、 caesium carbonate 、 碘甲烷 作用下， 以 四氢呋喃 、 乙醇 、 乙腈 为溶剂， 生成 3-chloro-N-[(3S)-1-(2-fluoro-4-pyrrolidin-2-ylphenyl)-2-oxopyrrolidin-3-yl]-1H-indole-6-sulfonamide
  参考文献：
  名称：

  Structure and property based design of factor Xa inhibitors: Pyrrolidin-2-ones with aminoindane and phenylpyrrolidine P4 motifs

  摘要：

  The rational design, syntheses and evaluation of potent sulfonamidopyrrolidin-2-one-based factor Xa inhibitors incorporating aminoindane and phenylpyrrolidine P4 motifs are described. These series delivered highly potent anticoagulant compounds with excellent oral pharmacokinetic profiles; however, significant time dependant P450 inhibition was an issue for the aminoindane series, but this was not observed with the phenylpyrrolidine motif, which produced candidate quality molecules with potential for once-daily oral dosing in humans. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.131

文献信息

• Structure and property based design of factor Xa inhibitors: Pyrrolidin-2-ones with aminoindane and phenylpyrrolidine P4 motifs
  作者：Robert J. Young、Carl Adams、Mike Blows、David Brown、Cynthia L. Burns-Kurtis、Chuen Chan、Laiq Chaudry、Máire A. Convery、David E. Davies、Anne M. Exall、Graham Foster、John D. Harling、Eric Hortense、Stephanie Irvine、Wendy R. Irving、Steve Jackson、Savvas Kleanthous、Anthony J. Pateman、Angela N. Patikis、Theresa J. Roethka、Stefan Senger、Gary J. Stelman、John R. Toomey、Robert I. West、Caroline Whittaker、Ping Zhou、Nigel S. Watson

  DOI：10.1016/j.bmcl.2011.01.131

  日期：2011.3

  The rational design, syntheses and evaluation of potent sulfonamidopyrrolidin-2-one-based factor Xa inhibitors incorporating aminoindane and phenylpyrrolidine P4 motifs are described. These series delivered highly potent anticoagulant compounds with excellent oral pharmacokinetic profiles; however, significant time dependant P450 inhibition was an issue for the aminoindane series, but this was not observed with the phenylpyrrolidine motif, which produced candidate quality molecules with potential for once-daily oral dosing in humans. (C) 2011 Elsevier Ltd. All rights reserved.