8-[4-({[({2-[(Bromoacetyl)amino]ethyl}amino)carbonyl]methyl}oxy)phenyl]-1,3-dipropylxanthine

• 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: 8-[4-({[({2-[(Bromoacetyl)amino]ethyl}amino)carbonyl]methyl}oxy)phenyl]-1,3-dipropylxanthine
• 英文别名: N-[2-(2-Bromo-acetylamino)-ethyl]-2-[4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-phenoxy]-acetamide；N-[2-[(2-bromoacetyl)amino]ethyl]-2-[4-(2,6-dioxo-1,3-dipropyl-7H-purin-8-yl)phenoxy]acetamide
• 化学式: C₂₃H₂₉BrN₆O₅
• 分子量: 549.424
• InChiKey: UBCFRLRABDBVAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  137
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  溴代乙酸酐 、 3,7-二乙基-9-(4-(N-2-氨基乙基甲酰氨基甲氧基))苯基黄嘌呤 在 N-甲基吗啉 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以93%的产率得到8-[4-({[({2-[(Bromoacetyl)amino]ethyl}amino)carbonyl]methyl}oxy)phenyl]-1,3-dipropylxanthine
  参考文献：
  名称：

  Electrophilic derivatives of purines as irreversible inhibitors of A1 adenosine receptors

  摘要：

  Functionalized congeners derived from 1,3-dipropyl-8-phenylxanthine and from N6-phenyladenosine were derivatized to contain electrophilic groups (isothiocyanate, N-hydroxysuccinimide ester, maleimide, sulfonyl chloride, or alpha-haloacyl group) capable of reaction with nucleophiles on biopolymers. The goal was to inhibit chemically the A1 adenosine receptor by using reactive agonist and antagonist ligands. Some of the electrophilic derivatives were synthesized through acylation of amine-functionalized congeners using hetero- or homobifunctional reagents available for protein cross-linking. The affinity for A1 adenosine receptors was evaluated in competitive binding assays by using rat and bovine brain membranes. Several xanthine and adenosine thiourea derivatives prepared from 1,3- and 1,4-phenylene diisothiocyanate (DITC) were potent irreversible inhibitors of adenosine receptors. Derivatives of m-DITC, at concentrations between 10 and 500 nM, irreversibly eliminated binding at 90% of the A1-receptor sites. Receptor affinity of both xanthine and adenosine derivatives containing distal phenylthiourea substituents was diminished by electron-donating groups on the ring.

  DOI：

  10.1021/jm00125a019

文献信息

• Electrophilic derivatives of purines as irreversible inhibitors of A1 adenosine receptors
  作者：Kenneth A. Jacobson、Suzanne Barone、Udai Kammula、Gary L. Stiles

  DOI：10.1021/jm00125a019

  日期：1989.5

  Functionalized congeners derived from 1,3-dipropyl-8-phenylxanthine and from N6-phenyladenosine were derivatized to contain electrophilic groups (isothiocyanate, N-hydroxysuccinimide ester, maleimide, sulfonyl chloride, or alpha-haloacyl group) capable of reaction with nucleophiles on biopolymers. The goal was to inhibit chemically the A1 adenosine receptor by using reactive agonist and antagonist ligands. Some of the electrophilic derivatives were synthesized through acylation of amine-functionalized congeners using hetero- or homobifunctional reagents available for protein cross-linking. The affinity for A1 adenosine receptors was evaluated in competitive binding assays by using rat and bovine brain membranes. Several xanthine and adenosine thiourea derivatives prepared from 1,3- and 1,4-phenylene diisothiocyanate (DITC) were potent irreversible inhibitors of adenosine receptors. Derivatives of m-DITC, at concentrations between 10 and 500 nM, irreversibly eliminated binding at 90% of the A1-receptor sites. Receptor affinity of both xanthine and adenosine derivatives containing distal phenylthiourea substituents was diminished by electron-donating groups on the ring.