5-(5-chloro-2-thienyl)-1,3-thiazole-2-sulfonyl chloride | 935458-28-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(5-chloro-2-thienyl)-1,3-thiazole-2-sulfonyl chloride
• 英文别名: 5-(5-Chlorothiophen-2-yl)-1,3-thiazole-2-sulfonyl chloride
• CAS: 935458-28-9
• 化学式: C₇H₃Cl₂NO₂S₃
• 分子量: 300.21
• InChiKey: YXLQQJZOAZBWNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  112
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S)-3-amino-1-[(1S)-1-methyl-2-(morpholin-4-yl)-2-oxoethyl]pyrrolidin-2-one 、 5-(5-chloro-2-thienyl)-1,3-thiazole-2-sulfonyl chloride 以140 mg的产率得到5-(5-chlorothiophen-2-yl)-N-[(3S)-1-[(2S)-1-(morpholin-4-yl)-1-oxopropan-2-yl]-2-oxopyrrolidin-3-yl]-1,3-thiazole-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：

  5-(5-chloro-2-thienyl)-1,3-thiazole 在 正丁基锂 、 二氧化硫 、 N-氯代丁二酰亚胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 0.33h， 生成 5-(5-chloro-2-thienyl)-1,3-thiazole-2-sulfonyl chloride
  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

• Structure and property based design of factor Xa inhibitors: Biaryl pyrrolidin-2-ones incorporating basic heterocyclic motifs
  作者：Robert J. Young、Alan D. Borthwick、David Brown、Cynthia L. Burns-Kurtis、Matthew Campbell、Chuen Chan、Marie Charbaut、Máire A. Convery、Hawa Diallo、Eric Hortense、Wendy R. Irving、Henry A. Kelly、N. Paul King、Savvas Kleanthous、Andrew M. Mason、Anthony J. Pateman、Angela N. Patikis、Ivan L. Pinto、Derek R. Pollard、Stefan Senger、Gita P. Shah、John R. Toomey、Nigel S. Watson、Helen E. Weston、Ping Zhou

  DOI：10.1016/j.bmcl.2007.11.019

  日期：2008.1

  Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating basic biaryl P4 groups, producing highly potent inhibitors with significant anticoagulant activities and encouraging oral pharmacokinetic profiles.