phenyl>acetic acid | 96760-57-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: phenyl>acetic acid
• 英文别名: N6-[4-(carboxymethyl)phenyl]adenosine；{p-[(9-β-D-ribofuranosyl-9H-purin-6-yl)amino]phenyl}acetic acid；Adenosine, N-phenylacetic acid；2-[4-[[9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-6-yl]amino]phenyl]acetic acid
• CAS: 96760-57-5
• 化学式: C₁₈H₁₉N₅O₆
• 分子量: 401.379
• InChiKey: GDUNTDCJAUFXGG-XKLVTHTNSA-N

物化性质

• 沸点：
  791.1±70.0 °C(Predicted)
• 密度：
  1.73±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  163
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  phenyl>acetic acid 在 N-乙基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 腺苷胺类
  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
• 作为产物：
  描述：

  对氨基苯乙酸 、 6-氯嘌呤核苷 在 三乙胺 作用下， 以 乙醇 、 水 为溶剂， 反应 72.0h， 以51%的产率得到phenyl>acetic acid
  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.
• Binary drugs: conjugates of purines and a peptide that bind to both adenosine and substance P receptors
  作者：Kenneth A. Jacobson、Andrzej W. Lipkowski、Terry W. Moody、William Padgett、Evelyn Pijl、Kenneth L. Kirk、John W. Daly

  DOI：10.1021/jm00391a046

  日期：1987.8

  A "functionalized congener" approach to adenosine receptor antagonists has provided a means to synthesize highly potent peptide conjugates of 1,3-dialkylxanthines. The antagonist XAC, such a functionalized xanthine amine congener, has been attached to a segment derived from the neurotransmitter peptide substance P (SP) to form a binary drug that binds to both receptors with Ki values of 35 nM (central A1-adenosine) and 300 nM (striatal SP). Coupling of the functionalized adenosine agonist N6-[p-(carboxymethyl)phenyl]adenosine to an SP C-terminal peptide also resulted in a binary drug that binds to both receptors. The demonstration that the biochemical properties of two unrelated drugs, both of which act through binding at extracellular receptors, may be combined in the same molecule suggests a novel strategy for drug design. In principle, a combined effect of the two different substances that produce the same final effect (e.g., hypotension by adenosine agonists and by SP analogues) might occur in vivo. Adenosine analogues have analgesic properties, and the binary drug derived from substance P and adenosine agonists or antagonists might provide useful tools for probing interrelationships of SP pathways and sites for the antinociceptive action of adenosine.
• Jacobson, Kenneth A.; Pannell, Lewis K.; Kirk, Kenneth L., Journal of the Chemical Society. Perkin transactions I, 1986, p. 2143 - 2150
  作者：Jacobson, Kenneth A.、Pannell, Lewis K.、Kirk, Kenneth L.、Fales, Henry M.、Sokoloski, Edward A.

  DOI：——

  日期：——
• JACOBSON, K. A.;LIPKOWSKI, A. W.;MOODY, T. W.;PADGETT, W.;PIJL, E.;KIRK, +, J. MED. CHEM., 30,(1987) N 8, 1529-1532
  作者：JACOBSON, K. A.、LIPKOWSKI, A. W.、MOODY, T. W.、PADGETT, W.、PIJL, E.、KIRK, +

  DOI：——

  日期：——
• EP0991414A4
  申请人：——

  公开号：EP0991414A4

  公开（公告）日：2002-10-02