4-Fluorosulfonyl-benzoic acid 3-(8-cyclopentyl-2,6-dioxo-3-propyl-2,3,6,7-tetrahydro-purin-1-yl)-propyl ester | 156547-57-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 4-Fluorosulfonyl-benzoic acid 3-(8-cyclopentyl-2,6-dioxo-3-propyl-2,3,6,7-tetrahydro-purin-1-yl)-propyl ester
• 英文别名: 3-(8-cyclopentyl-2,6-dioxo-3-propyl-7H-purin-1-yl)propyl 4-fluorosulfonylbenzoate
• CAS: 156547-57-8
• 化学式: C₂₃H₂₇FN₄O₆S
• 分子量: 506.555
• InChiKey: XMBCEKSLDYYQEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  8-cyclopentyl-1-(3-hydroxypropyl)-3-propylxanthine 、 4-(氟磺酰)苯酰氯 以 1,4-二氧六环 为溶剂， 反应 12.0h， 以76%的产率得到4-Fluorosulfonyl-benzoic acid 3-(8-cyclopentyl-2,6-dioxo-3-propyl-2,3,6,7-tetrahydro-purin-1-yl)-propyl ester
  参考文献：
  名称：

  Substituted 1,3-Dipropylxanthines as Irreversible Antagonists of A1 Adenosine Receptors

  摘要：

  This report describes the synthesis of 29 xanthines containing a chemoreactive chloroaryl beta-chloroethylamino, alpha,beta-unsaturated carbonyl bromoacetyl, 3-(fluorosulfonyl)benzoyl, or 4-(fluorosulfonyl)benzoyl group as part of an exocyclic 1-, 3-, or 8-substituent. The xanthines inhibited the binding of [H-3]-8-cyclopentyl-1,3-dipropylxanthine ([H-3]CPX) to the A(1) adenosine receptor (A(1)AR) of DDT1 MF2 cells at IC(50)s in the low-nanomolar to low-micromolar range. Seven of the 29 analogues irreversibly inhibited the binding of [H-3]CPX without changing the K-D of that ligand; five were 1,3-dipropylxantines having the following reactive groups as 8-substituents: (bromoacetamido)methyl (24), (bromoacetamido)ethyl (25), (bromoacetamido)propyl (26), [4-(fluorosulfonyl)benzamido]methyl (33) or 3-[[4-(fluorosulfonyl)benzoyl]oxy]cyclopentyl (42). Both 8-cyclopentyl-3-[3-[[4-(fluorosulfonyl)benzoyl]oxy]propyl]-1-propylxanthine (53) and 8-cyclopentyl-3-bis[3-[[4-(fluorosulfonyl)benzoyl]oxy]propyl]xanthine (55) inhibited [H-3]CPX binding irreversibly. Five of the ligands, including 26, 33 (IC50 = 49 mu M), and 53 (IC50 = 9 mu M), antagonized the binding of [H-3]NECA to the A(2a)AR of PC12 cells, but unlike binding to the A(1)AR, binding to the A(2a)AR was completely reversible. The potency of 33 (IC50 = 2 mu M, 72% loss of CPX binding at 1 mu M) and 53 (IC50 - 0.01 mu M, 74% loss of CPX binding at 0.05 mu M) and their seletivity for the A(1)AR suggest that those two ligands may be useful in studies of the structure and function of that receptor.

  DOI：

  10.1021/jm00043a010

文献信息

• Scammells Peter J., Baker Stephen P., Belardinelli Luiz, Olsson Ray A., J. Med. Chem, 37 (1994) N 17, S 2704-2712
  作者：Scammells Peter J., Baker Stephen P., Belardinelli Luiz, Olsson Ray A.

  DOI：——

  日期：——
• Substituted 1,3-Dipropylxanthines as Irreversible Antagonists of A1 Adenosine Receptors
  作者：Peter J. Scammells、Stephen P. Baker、Luiz Belardinelli、Ray A. Olsson

  DOI：10.1021/jm00043a010

  日期：1994.8

  This report describes the synthesis of 29 xanthines containing a chemoreactive chloroaryl beta-chloroethylamino, alpha,beta-unsaturated carbonyl bromoacetyl, 3-(fluorosulfonyl)benzoyl, or 4-(fluorosulfonyl)benzoyl group as part of an exocyclic 1-, 3-, or 8-substituent. The xanthines inhibited the binding of [H-3]-8-cyclopentyl-1,3-dipropylxanthine ([H-3]CPX) to the A(1) adenosine receptor (A(1)AR) of DDT1 MF2 cells at IC(50)s in the low-nanomolar to low-micromolar range. Seven of the 29 analogues irreversibly inhibited the binding of [H-3]CPX without changing the K-D of that ligand; five were 1,3-dipropylxantines having the following reactive groups as 8-substituents: (bromoacetamido)methyl (24), (bromoacetamido)ethyl (25), (bromoacetamido)propyl (26), [4-(fluorosulfonyl)benzamido]methyl (33) or 3-[[4-(fluorosulfonyl)benzoyl]oxy]cyclopentyl (42). Both 8-cyclopentyl-3-[3-[[4-(fluorosulfonyl)benzoyl]oxy]propyl]-1-propylxanthine (53) and 8-cyclopentyl-3-bis[3-[[4-(fluorosulfonyl)benzoyl]oxy]propyl]xanthine (55) inhibited [H-3]CPX binding irreversibly. Five of the ligands, including 26, 33 (IC50 = 49 mu M), and 53 (IC50 = 9 mu M), antagonized the binding of [H-3]NECA to the A(2a)AR of PC12 cells, but unlike binding to the A(1)AR, binding to the A(2a)AR was completely reversible. The potency of 33 (IC50 = 2 mu M, 72% loss of CPX binding at 1 mu M) and 53 (IC50 - 0.01 mu M, 74% loss of CPX binding at 0.05 mu M) and their seletivity for the A(1)AR suggest that those two ligands may be useful in studies of the structure and function of that receptor.