(3S)-3-{[(6-chloro-1,3-benzothiazol-2-yl)thio]amino}-1-[(1S)-1-methyl-2-(morpholin-4-yl)-2-oxoethyl]pyrrolidin-2-one | 478646-03-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3S)-3-{[(6-chloro-1,3-benzothiazol-2-yl)thio]amino}-1-[(1S)-1-methyl-2-(morpholin-4-yl)-2-oxoethyl]pyrrolidin-2-one
• 英文别名: (3S)-3-[(6-chloro-1,3-benzothiazol-2-yl)sulfanylamino]-1-[(2S)-1-morpholin-4-yl-1-oxopropan-2-yl]pyrrolidin-2-one
• CAS: 478646-03-6
• 化学式: C₁₈H₂₁ClN₄O₃S₂
• 分子量: 440.975
• InChiKey: BBVSJLZFKNXMDN-FZMZJTMJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3S)-3-{[(6-chloro-1,3-benzothiazol-2-yl)thio]amino}-1-[(1S)-1-methyl-2-(morpholin-4-yl)-2-oxoethyl]pyrrolidin-2-one 在 potassium permanganate 作用下， 以 丙酮 为溶剂， 反应 21.0h， 以6%的产率得到6-chloro-N-[(3S)-1-[(2S)-1-(morpholin-4-yl)-1-oxopropan-2-yl]-2-oxopyrrolidin-3-yl]-1,3-benzothiazole-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 N-氯代丁二酰亚胺 、 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 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.5h， 生成 (3S)-3-{[(6-chloro-1,3-benzothiazol-2-yl)thio]amino}-1-[(1S)-1-methyl-2-(morpholin-4-yl)-2-oxoethyl]pyrrolidin-2-one
  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

• Pyrrolidine derivatives as factor xa inhibitors
  申请人：Chan Chuen

  公开号：US20050107379A1

  公开（公告）日：2005-05-19

  The invention relates to compounds of formula (I) 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.

  本发明涉及公式（I）的化合物、其制备方法、包含它们的药物组合物以及它们在医学中的使用，特别是在改善需要使用Xa因子抑制剂的临床病情方面的使用。
• 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。
• Pyrrolidin-2-one derivatives as inhibitors of factor xa
  申请人：——

  公开号：US20040152697A1

  公开（公告）日：2004-08-05

  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. 1

  本发明涉及公式（Ic）化合物，它们的制备过程，含有它们的药物组合物，以及它们在医学上的应用，特别是在改善适合使用因子Xa抑制剂的临床症状方面的应用。
• PYRROLIDINE DERIVATIVES AS FACTOR XA INHIBITORS
  申请人：CHAN Chuen

  公开号：US20070142374A1

  公开（公告）日：2007-06-21

  The invention relates to compounds of formula (I) 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(I)的化合物，其制备方法，包含它们的药物组合物以及它们在医学上的使用，特别是在改善需要使用因子Xa抑制剂的临床病情方面的使用。
• Chemicals compounds
  申请人：GLAXO GROUP LIMITED

  公开号：EP1839659A2

  公开（公告）日：2007-10-03

  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) 的化合物 的制备工艺、含有它们的药物组合物以及它们在医学中的用途，特别是在改善Xa因子抑制剂适用的临床症状中的用途。