8-(4'-Carboxymethyloxyphenyl)-1,3-dipropylxanthine ethyl ester | 96865-87-1

• 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 ethyl ester
• 英文别名: ethyl 2-[4-(2,6-dioxo-1,3-dipropyl-7H-purin-8-yl)phenoxy]acetate
• CAS: 96865-87-1
• 化学式: C₂₁H₂₆N₄O₅
• 分子量: 414.461
• InChiKey: MVDJCRHMFYMNMB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  8-(4'-Carboxymethyloxyphenyl)-1,3-dipropylxanthine ethyl ester 在 氢溴酸 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-2,6-Diamino-hexanoic acid (2-{2-[4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-phenoxy]-acetylamino}-ethyl)-amide; hydrobromide
  参考文献：
  名称：

  Xanthine functionalized congeners as potent ligands at A2-adenosine receptors

  摘要：

  Amide derivatives of a carboxylic acid congener of 1,3-dialkylxanthine, having a 4-[(carboxymethyl)oxy]phenyl substituent at the 8-position, have been synthesized in order to identify potent antagonists at A2-adenosine receptors stimulatory to adenylate cyclase in platelets. Distal structural features of amide-linked chains and the size of the 1,3-dialkyl groups have been varied. 1,3-Diethyl groups, more than 1,3-dimethyl or 1,3-dipropyl groups, favor A2 potency, even in the presence of extended chains attached at the 8-(p-substituted-phenyl) position. Polar groups, such as amines, on the chain simultaneously enhance water solubility and A2 potency. Among the most potent A2 ligands are an amine congener, 8-[4-[[[[(2-aminoethyl)amino]carbonyl]methyl]oxy]phenyl]- 1,3-diethylxanthine, and its D-lysyl conjugate, which have KB values of 21 and 23 nM, respectively, for the antagonism of N-ethyl-adenosine-5'-uronamide-stimulated adenylate cyclase activity in human platelet membranes. Strategies for the selection and tritiation of new radioligands for use in competitive binding assays at A2-adenosine receptors have been considered.

  DOI：

  10.1021/jm00384a037
• 作为产物：
  描述：

  8-(4-羧甲基氧基)苯基-1,3-二丙基黄嘌呤 在 三氯化铁 作用下， 以 乙醇 为溶剂， 以1.27 g (70.8%)的产率得到8-(4'-Carboxymethyloxyphenyl)-1,3-dipropylxanthine ethyl ester
  参考文献：
  名称：

  Biologically-active 1,3-dipropyl-8-phenylxanthine derivatives

  摘要：

  某些功能化的1,3-二烷基黄嘌呤衍生物作为A.sub.1-和A.sub.2-腺苷受体的拮抗剂表现出高效性和选择性，并适合连接到探针、药物载体或固体支持物上。这些衍生物的特点是在8位置带有苯基，对位取代为功能化链以提供高水溶性和高受体亲和力，使得这些化合物适合用作抗过敏、抗哮喘或强心药、中枢神经系统兴奋剂和利尿剂。

  公开号：

  US04612315A1

文献信息

• Functionalized congeners of 1,3-dialkylxanthines: preparation of analogs with high affinity for adenosine receptors
  作者：Kenneth A. Jacobson、Kenneth L. Kirk、William L. Padgett、John W. Daly

  DOI：10.1021/jm00147a038

  日期：1985.9

  receptor antagonists. On the basis of the high potency of 8-(p-hydroxyphenyl)-1,3-dialkylxanthines, the parent compounds were 8-[4-[(carboxymethyl)oxy]phenyl] derivatives of theophylline and 1,3-dipropylxanthine. A series of analogues including esters of ethanol and N-hydroxysuccinimide, amides, a hydrazide, an acylurea, and anilides were prepared. The potency in blocking A1-adenosine receptors (inhibition

  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。
• Biologically-active xanthine derivatives
  申请人：The United States of America as represented by the Department of Health

  公开号：US04696932A1

  公开（公告）日：1987-09-29

  Certain functionalized cogeners of 1,3-dialkylxanthine exhibit high potency and selectivity as antagonists for A.sub.1 - and A.sub.2 -adenosine receptors and are suitable for attachment to probes, drug carriers, or solid supports. These derivatives are characterized by the presence of a phenyl at the 8 position para-substituted with a functionalized chain to provide high water solubility and high receptor affinity. Some of these analogs, containing a distal amino- or carboxylic-functionalized chain, are suitable for synthesis of amino acid conjugates. The compounds of this invention are suitable for use as antiallergenic, antiasthmatic, or cardiotonic drugs, central nervous system stimulants, and diuretics.

  1,3-二烷基黄嘌呤的某些官能化同系物表现出高效和选择性，作为A.sub.1-和A.sub.2-腺苷受体的拮抗剂，并适合附着到探针、药物载体或固体支撑物上。这些衍生物的特点是在8位存在一个苯基，对位取代一个官能化链以提供高水溶性和高受体亲和力。其中一些含有远端氨基或羧基官能化链的类似物，适合用于合成氨基酸共轭物。本发明的化合物适用于用作抗过敏、抗哮喘或心脏强心药、中枢神经系统兴奋剂和利尿剂。
• 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