8-(4'-Carboxymethyloxyphenyl)-1,3-dipropylxanthine N-hydroxysuccinimide ester

• 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'-Carboxymethyloxyphenyl)-1,3-dipropylxanthine N-hydroxysuccinimide ester
• 英文别名: [4-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-phenoxy]-acetic acid 2,5-dioxo-pyrrolidin-1-yl ester；(2,5-dioxopyrrolidin-1-yl) 2-[4-(2,6-dioxo-1,3-dipropyl-7H-purin-8-yl)phenoxy]acetate
• 化学式: C₂₃H₂₅N₅O₇
• 分子量: 483.481
• InChiKey: NPCYZVFLXAHEOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  142
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-甲酰苯氧基乙酸 在 三氯化铁 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.25h， 生成 8-(4'-Carboxymethyloxyphenyl)-1,3-dipropylxanthine N-hydroxysuccinimide ester
  参考文献：
  名称：

  1,3-二烷基黄嘌呤的功能化同系物：制备对腺苷受体具有高亲和力的类似物。

  摘要：

  一系列功能化的 1,3-二烷基黄嘌呤同源物已被制备作为腺苷受体拮抗剂。基于8-(对羟基苯基)-1,3-二烷基黄嘌呤的高效力，母体化合物是茶碱和1,3-二丙基黄嘌呤的8-[4-[(羧甲基)氧基]苯基]衍生物。制备了一系列类似物，包括乙醇和N-羟基琥珀酰亚胺的酯、酰胺、酰肼、酰基脲和苯胺。阻断 A1-腺苷受体（抑制 N6-[3H]环己基腺苷与脑膜的结合）和 A2-腺苷受体（抑制 2-氯腺苷引起的脑切片中环 AMP 积累）的效力受到结构变化的显着影响位于主要药效基团（8-苯基-1,3-二烷基黄嘌呤）的远端。二丙基系列对 A1 受体的效力范围从具有末端酰胺基乙烯胺部分的同源物的 Ki 值 1.2 nM，到母体羧酸的 Ki 值 58 nM，再到庞大的脲基同源物的 Ki 值 96 nM。某些同系物对 A1 受体的活性比对 A2 受体的活性高 145 倍。同系物的各种衍生物应可用作受体探针并用于放射性碘标记、抗生物素蛋白结合和亲和柱的制备。

  DOI：

  10.1021/jm00147a038

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.
• JACOBSON, KENNETH A.;BARONE, SUZANNE;KAMMULA, UDAI;STILES, GARY L., J. MED. CHEM., 32,(1989) N, C. 1043-1051
  作者：JACOBSON, KENNETH A.、BARONE, SUZANNE、KAMMULA, UDAI、STILES, GARY L.

  DOI：——

  日期：——
• EP0198921A4
  申请人：——

  公开号：EP0198921A4

  公开（公告）日：1987-03-16
• BIOLOGICALLY-ACTIVE XANTHINE DERIVATIVES
  申请人：UNITED STATES OF AMERICA, represented by THE UNITED STATES DEPARTMENT OF COMMERCE

  公开号：EP0198921A1

  公开（公告）日：1986-10-29
• US4612315A
  申请人：——

  公开号：US4612315A

  公开（公告）日：1986-09-16