t-butyl 5-chloro-2-[({(3S)-1-[(1S)-1-methyl-2-(morpholin-4-yl)-2-oxoethyl]-2-oxopyrrolidin-3-yl}amino)sulfonyl]-1H-indole-1-carboxylate | 478645-99-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: t-butyl 5-chloro-2-[({(3S)-1-[(1S)-1-methyl-2-(morpholin-4-yl)-2-oxoethyl]-2-oxopyrrolidin-3-yl}amino)sulfonyl]-1H-indole-1-carboxylate
• 英文别名: tert-butyl 5-chloro-2-[[(3S)-1-[(2S)-1-morpholin-4-yl-1-oxopropan-2-yl]-2-oxopyrrolidin-3-yl]sulfamoyl]indole-1-carboxylate
• CAS: 478645-99-7
• 化学式: C₂₄H₃₁ClN₄O₇S
• 分子量: 555.052
• InChiKey: SMNRDBQOIOHWDW-YJBOKZPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  136
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  t-butyl 5-chloro-2-[({(3S)-1-[(1S)-1-methyl-2-(morpholin-4-yl)-2-oxoethyl]-2-oxopyrrolidin-3-yl}amino)sulfonyl]-1H-indole-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以91%的产率得到5-Chloro-N-{(3s)-1-[(1s)-1-Methyl-2-Morpholin-4-Yl-2-5-Chloro-N-{(3s)-1-[(1s)-1-Methyl-2-Morpholin-4-Yl-2-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 palladium on activated charcoal 吡啶 、 氢气 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 t-butyl 5-chloro-2-[({(3S)-1-[(1S)-1-methyl-2-(morpholin-4-yl)-2-oxoethyl]-2-oxopyrrolidin-3-yl}amino)sulfonyl]-1H-indole-1-carboxylate
  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

文献信息

• Chemical compounds
  申请人：Chan Chuen

  公开号：US20060160886A1

  公开（公告）日：2006-07-20

  The invention relates to compounds of formula (Ic) processes for their preparation, pharmaceutical compositions containing them and to their use in medicine, particularly use in the amelioration of a clinical condition for which a Factor Xa inhibitor is indicated.

  本发明涉及式(Ic)化合物，其制备方法，含有它们的药物组合物以及它们在医学上的应用，特别是在改善适应于Xa因子抑制剂的临床状况方面的应用。
• US7282497B2
  申请人：——

  公开号：US7282497B2

  公开（公告）日：2007-10-16
• Factor Xa Inhibitors:  S1 Binding Interactions of a Series of <i>N</i>-{(<i>3S</i>)-1-[(<i>1S</i>)-1-Methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides
  作者：Chuen Chan、Alan D. Borthwick、David Brown、Cynthia L. Burns-Kurtis、Matthew Campbell、Laiq Chaudry、Chun-wa Chung、Máire A. Convery、J. Nicole Hamblin、Lisa Johnstone、Henry A. Kelly、Savvas Kleanthous、Angela Patikis、Champa Patel、Anthony J. Pateman、Stefan Senger、Gita P. Shah、John R. Toomey、Nigel S. Watson、Helen E. Weston、Caroline Whitworth、Robert J. Young、Ping Zhou

  DOI：10.1021/jm060870c

  日期：2007.4.1

  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.