4-(1,3-二甲基-2,6-二氧代-2,3,6,9-四氢-1H-嘌呤-8-基)苯甲酸 | 85872-58-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 4-(1,3-二甲基-2,6-二氧代-2,3,6,9-四氢-1H-嘌呤-8-基)苯甲酸
• 英文名称: 8-(4-carboxyphenyl)-1,3-dimethyl-3,7-dihydropurin-2,6-dione
• 英文别名: 4-(1,3-dimethyl-2,6-dioxo-1H-purin-8-yl)benzoic acid；4-(1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)-benzoic acid；4-(1,3-Dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)-benzoesaeure；Benzoic acid, 4-(2,3,6,7-tetrahydro-1,3-dimethyl-2,6-dioxo-1H-purin-8-yl)-；4-(1,3-dimethyl-2,6-dioxo-7H-purin-8-yl)benzoic acid
• CAS: 85872-58-8
• 化学式: C₁₄H₁₂N₄O₄
• 分子量: 300.274
• InChiKey: VOGIMZNURUXDIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-哌啶乙醇 、 4-(1,3-二甲基-2,6-二氧代-2,3,6,9-四氢-1H-嘌呤-8-基)苯甲酸 在 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 以58.7%的产率得到8-[4-[4-(2-hydroxyethyl)piperidinocarbonyl]phenyl]-1,3-dimethyl-3,7-dihydropurin-2,6-dione
  参考文献：
  名称：

  New 8-substituted xanthiene derivatives as potent bronchodilators

  摘要：

  The synthesis and structure determination of 8-aryl /alkyl aryl 1, 3-dimethyl-3, 7-dihydropurin-2, 6-dione derivatives (1-13), was carried out in this study. Bronchodilator activity is investigated using isolated guinea-pig tracheal strips, pre-contracted by acetylcholine and histamine. Spasmolytic activity of the compounds was compared to theophylline. Synthesized compounds (1-13) did not inhibit the acetylcholine-induced pre-contractions except compound (8) at 10(-5) M concentration. In contrast, some of the compounds, especially (7), (11), (12) at 10(-5) M and (3), (4), (9) and (11) in 10(-4) M displayed inhibitory activity on the tracheal strips pre-contracted by histamine. The potency of the compounds at human adenosine receptors was evaluated using radioligand binding assay and a cyclic AMP functional assay in CHO cells expressing these receptors. Compound (11) displayed the greatest activity against radioligand binding of specific agonists to A2A and A2B receptors. The compounds were relatively selective for both A2A and A2B compared with A1 and A3 receptors. All compounds were also tested for the inhibition of NECA-induced cAMP accumulation mediated by the A2B adenosine receptor and compound (11) was found to be the most effective. Our results showed that these compounds are acting as selective adenosine antagonists, especially for adenosine A2B receptors, and are promising as potent anti-inflammatory agents rather than bronchodilator for the treatment of asthma.

  DOI：

  10.1016/j.farmac.2005.08.011
• 作为产物：
  描述：

  6-amino-5-[(4-carboxybenzyliden)amino]-1,3-dimethyl-1H-pyrimidine-2,4-dione 在 三氯化铁 作用下， 以 乙醇 为溶剂， 以46%的产率得到4-(1,3-二甲基-2,6-二氧代-2,3,6,9-四氢-1H-嘌呤-8-基)苯甲酸
  参考文献：
  名称：

  1,3-二烷基-8-（对-磺基苯基）黄嘌呤：A1-和A2-腺苷受体的有效水溶性拮抗剂。

  摘要：

  评估了茶碱和其他1,3-二烷基黄嘌呤的一系列8-（取代苯基）衍生物作为脑组织中A1-和A2-腺苷受体拮抗剂的效能和选择性。茶碱对A1和A2受体的功效相似（Ki = 14 microM）。作为腺苷受体拮抗剂，8-苯基茶碱的功效比茶碱高25-35倍，而8-苯基咖啡因的功效仅比咖啡因高2-3倍。对羟基芳基取代基增强了8-苯基茶碱作为腺苷拮抗剂的效力。对-羧基和对-硫芳基取代基降低了8-苯基茶碱的效力，产生了水溶性腺苷拮抗剂，在腺苷受体上，它们的效力比茶碱大2-5倍。8-（取代的苯基）茶碱均没有特别选择性地作为对A1-和A2-腺苷受体的拮抗剂。1,3-二丙基-8-苯基黄嘌呤代表一种有效的和选择性的A1受体拮抗剂，在A1受体上的效力比在A2受体上高约23倍。对羟基芳基取代基进一步增强了1,3-二丙基-8-苯基黄嘌呤在A1和A2受体上的效力。8-（2-氨基-4-氯苯基）-1,3-二丙基黄嘌呤是A1受体

  DOI：

  10.1021/jm00382a018

文献信息

• 1,3-Dialkyl-8-(p-sulfophenyl)xanthines: potent water-soluble antagonists for A1- and A2-adenosine receptors
  作者：John W. Daly、W. Padgett、M. T. Shamim、P. Butts-Lamb、J. Waters

  DOI：10.1021/jm00382a018

  日期：1985.4

  further enhances potency of the 1,3-dipropyl-8-phenylxanthine at both A1 and A2 receptors. The 8-(2-amino-4-chlorophenyl)-1,3-dipropylxanthine is a very potent and selective antagonist for A1 receptors, being nearly 400-fold more potent at A1 than at A2 receptors. The water-soluble 8-(p-sulfophenyl)- and 8-(p-carboxyphenyl)-1,3-propylxanthines no longer exhibit marked selectivity. Both compounds are

  评估了茶碱和其他1,3-二烷基黄嘌呤的一系列8-（取代苯基）衍生物作为脑组织中A1-和A2-腺苷受体拮抗剂的效能和选择性。茶碱对A1和A2受体的功效相似（Ki = 14 microM）。作为腺苷受体拮抗剂，8-苯基茶碱的功效比茶碱高25-35倍，而8-苯基咖啡因的功效仅比咖啡因高2-3倍。对羟基芳基取代基增强了8-苯基茶碱作为腺苷拮抗剂的效力。对-羧基和对-硫芳基取代基降低了8-苯基茶碱的效力，产生了水溶性腺苷拮抗剂，在腺苷受体上，它们的效力比茶碱大2-5倍。8-（取代的苯基）茶碱均没有特别选择性地作为对A1-和A2-腺苷受体的拮抗剂。1,3-二丙基-8-苯基黄嘌呤代表一种有效的和选择性的A1受体拮抗剂，在A1受体上的效力比在A2受体上高约23倍。对羟基芳基取代基进一步增强了1,3-二丙基-8-苯基黄嘌呤在A1和A2受体上的效力。8-（2-氨基-4-氯苯基）-1,3-二丙基黄嘌呤是A1受体
• Effects of 8-phenyl and 8-cycloalkyl substituents on the activity of mono-, di, and trisubstituted alkylxanthines with substitution at the 1-, 3-, and 7-positions
  作者：Mah T. Shamim、Dieter Ukena、William L. Padgett、John W. Daly

  DOI：10.1021/jm00126a014

  日期：1989.6

  The effects of 8-phenyl and 8-cycloalkyl substituents on the activity of theophylline, caffeine, 1,3-dipropylxanthine, 1,3-dipropyl-7-methylxanthine, 3-propylxanthine, and 1-propylxanthine at A1 adenosine receptors of rat brain and fat cells and at A2 adenosine receptors of rat pheochromocytoma PC12 cells and human platelets are compared. An 8-phenyl substituent has little effect on the activity of

  8-苯基和8-环烷基取代基对大鼠脑A1腺苷受体上茶碱，咖啡因，1,3-二丙基黄嘌呤，1,3-二丙基-7-甲基黄嘌呤，3-丙基黄嘌呤和1-丙基黄嘌呤活性的影响比较了大鼠嗜铬细胞瘤PC12细胞和人血小板的脂肪细胞和A2腺苷受体。8-苯基取代基对咖啡因或1,3-二丙基-7-甲基黄嘌呤在腺苷受体上的活性几乎没有影响，而茶碱，1,3-二丙基黄嘌呤，1-异戊基-3-异丁基黄嘌呤，1-甲基黄嘌呤和3-丙基黄嘌呤。8-苯基-1-丙基黄嘌呤在所有受体上均有效（Ki = 20-70 nM）。对羧基或对磺基取代基，它被引入8-苯环以增加水溶性，在大多数情况下，会降低A1受体的活性和选择性。在8-对-磺基类似物中，只有8-（对-磺基苯基）茶碱和1，3-二丙基-8-（对-磺基苯基）黄嘌呤对A1受体具有选择性。咖啡因，1，3-二丙基-7-甲基黄嘌呤和3-丙基黄嘌呤的8-对-磺基苯基衍生物对A2受体具有一定的选择性。8
• Exploration of polystyrene-supported 2-isobutoxy-1-isobutoxycarbonyl-1,2-dihydroquinoline (PS-IIDQ) as new coupling agent for the synthesis of 8-substituted xanthine derivatives
  作者：Prabal Bandyopadhyay、Manisha Sathe、Pratibha Sharma、M.P. Kaushik

  DOI：10.1016/j.tetlet.2012.04.135

  日期：2012.8

  Polystyrene-supported 2-isobutoxy-1-isobutoxycarbonyl-1,2-dihydroquinoline (PS-IIDQ), a polymer supported covalent coupling reagent, was successfully employed for the first time in the synthesis of 8-substituted xanthine derivatives. PS-IIDQ was observed to be more efficient than IIDQ and polymer-supported carbodiimide (PS-EDC). (C) 2012 Elsevier Ltd. All rights reserved.
• Kompis et al., Chemicke Zvesti, 1958, vol. 12, p. 519,521
  作者：Kompis et al.

  DOI：——

  日期：——
• HAMILTON, H. W.;ORTWINE, D. F.;WORTH, D. F.;BADGER, E. BRISTOL, J. A.;BRU+, J. MED. CHEM., 1985, 28, N 8, 1071-1079
  作者：HAMILTON, H. W.、ORTWINE, D. F.、WORTH, D. F.、BADGER, E. BRISTOL, J. A.、BRU+

  DOI：——

  日期：——