2-(8-溴-1,3-二甲基-2,6-二氧代嘌呤-7-基)乙醛 | 111038-29-0

• 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: 2-(8-溴-1,3-二甲基-2,6-二氧代嘌呤-7-基)乙醛
• 英文名称: 6-Bromotheophyllinyl-7-acetaldehyde
• 英文别名: 7-acetic-8-bromotheophylline aldehyde；2-(8-bromo-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)acetaldehyde；8-bromotheophylline-7-acetic aldehyde；7H-Purine-7-acetaldehyde, 1,2,3,6-tetrahydro-8-bromo-1,3-dimethyl-2,6-dioxo-；2-(8-bromo-1,3-dimethyl-2,6-dioxopurin-7-yl)acetaldehyde
• CAS: 111038-29-0
• 化学式: C₉H₉BrN₄O₃
• 分子量: 301.099
• InChiKey: SSTGBMCLNGQXNF-UHFFFAOYSA-N

物化性质

• 熔点：
  189-191 °C
• 沸点：
  484.6±55.0 °C(Predicted)
• 密度：
  1.87±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  75.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(8-溴-1,3-二甲基-2,6-二氧代嘌呤-7-基)乙醛 、 1-(3-氯苯基)哌嗪 以 乙二醇甲醚 为溶剂， 生成 8-[3-(N4-3'-chlorophenyl)-piperazin-N1-yl-propyl]-1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine-2,4-dione
  参考文献：
  名称：

  Serotonin transporter activity of imidazolidine-2,4-dione and imidazo[2,1-f]purine-2,4-dione derivatives in aspect of their acid–base properties

  摘要：

  Affinities of arylpiperazinylalkyl derivatives of imidazo[2,1-f]purine-2,4-dione and imidazolidine-2,4-dione for serotonin transporter and their acid-base properties were evaluated. The dissociation constant (pK (a)) of compounds 1-22 were determinated by potentiometric titration and calculated using pKalc 3.1 module of the Pallas system. The data from experimental methods and computational calculations were compared and suitable conclusions were reached.

  DOI：

  10.1007/s00044-011-9883-y
• 作为产物：
  描述：

  8-溴-7-(2,3-二羟基丙基)-1,3-二甲基嘌呤-2,6-二酮 在 过碘酸 作用下， 以 水 为溶剂， 反应 10.0h， 以70%的产率得到2-(8-溴-1,3-二甲基-2,6-二氧代嘌呤-7-基)乙醛
  参考文献：
  名称：

  Synthesis, transformations, and biological properties of 7,8-disubstituted xanthines

  摘要：

  DOI：

  10.1007/bf00757486

文献信息

• Synthesis and biological evaluation of 2-fluoro and 3-trifluoromethyl-phenyl-piperazinylalkyl derivatives of 1<i>H</i>-imidazo[2,1-<i>f</i>]purine-2,4(3<i>H</i>,8<i>H</i>)-dione as potential antidepressant agents
  作者：Agnieszka Zagórska、Adam Bucki、Marcin Kołaczkowski、Agata Siwek、Monika Głuch-Lutwin、Gabriela Starowicz、Grzegorz Kazek、Anna Partyka、Anna Wesołowska、Karolina Słoczyńska、Elżbieta Pękala、Maciej Pawłowski

  DOI：10.1080/14756366.2016.1198902

  日期：2016.11.3

  2-fluoro and 3-trifluoromethylphenylpiperazinylalkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione (4-21) were synthesized and evaluated for their serotonin (5-HT1A/5-HT7) receptor affinity and phosphodiesterase (PDE4B and PDE10A) inhibitor activity. The study enabled the identification of potent 5-HT1A, 5-HT7 and mixed 5-HT1A/5-HT7 receptor ligands with weak inhibitory potencies for PDE4B and PDE10A

  合成了一系列的1H-咪唑并[2,1-f]嘌呤-2,4（3H，8H）-二酮（4-21）的2-氟和3-三氟甲基苯基哌嗪基烷基衍生物，并对其5-羟色胺（5-HT1A）进行了评估/ 5-HT7）受体亲和力和磷酸二酯酶（PDE4B和PDE10A）抑制剂的活性。该研究能够鉴定出对PDE4B和PDE10A具有弱抑制能力的有效5-HT1A，5-HT7和混合的5-HT1A / 5-HT7受体配体。已经使用胶束电动色谱（MEKC）系统和人肝微粒体（HLM）模型确定了亲脂性和代谢稳定性，从而完成了测试。在体内初步药理研究中，选择化合物8-（5-（4-（2-氟苯基）哌嗪-1-基）戊基）-1,3,7-三甲基-1H-咪唑并[2,1-f]嘌呤-2,4（3H，8H）-二酮（9）在小鼠的强迫游泳试验（FST）中表现为潜在的抗抑郁药。此外，由9引起的抗焦虑作用（2.5 mg / kg）要大于参考抗焦虑药地西epa。分子建模表明，1H-咪唑并[2
• Characteristics of metabolic stability and the cell permeability of 2‐pyrimidinyl‐piperazinyl‐alkyl derivatives of 1H‐imidazo[2,1 <i>‐f</i> ]purine‐2,4(3 <i>H</i> ,8 <i>H</i> )‐dione with antidepressant‐ and anxiolytic‐like activities
  作者：Agnieszka Zagórska、Anna Partyka、Adam Bucki、Marcin Kołaczkowski、Magdalena Jastrzębska‐Więsek、Anna Czopek、Agata Siwek、Monika Głuch‐Lutwin、Marek Bednarski、Marek Bajda、Jakub Jończyk、Kamil Piska、Paulina Koczurkiewicz、Anna Wesołowska、Maciej Pawłowski

  DOI：10.1111/cbdd.13442

  日期：2019.4

  antagonist of 5-HT1A . Molecular modeling studies revealed differences in binding mode between compound 4b and buspirone, which might reflect variation of the ligands' affinity and potency in the 5-HT1A receptor. Compound 4b in silico models demonstrated drug-likeness properties and, contrary to buspirone, showed a metabolic stability in mouse liver microsomes system. Experimentally obtained value

  为了发现一类新型的精神药物，已经合成了一系列的1H-咪唑并[2,1-f]嘌呤-2,4（3H，8H）-二酮的2-嘧啶基-哌嗪基-烷基衍生物。评价化合物对5-羟色胺5-HT1A，5-HT7和磷酸二酯酶PDE4和PDE10的体外亲和力。最有效的化合物2-嘧啶基-1-哌嗪基丁基-咪唑并[2,1-f]嘌呤-2,4-二酮（4b）是5-HT1A的强效选择性拮抗剂。分子模型研究表明，化合物4b与丁螺环酮之间的结合方式不同，这可能反映了5HT1A受体中配体亲和力和效力的变化。在计算机模拟模型中，化合物4b表现出药物相似性，并且与丁螺环酮相反，在小鼠肝微粒体系统中表现出代谢稳定性。在平行人工渗透率测定中，实验获得的4b的表观渗透率系数Papp值表明与血浆蛋白弱结合和高肠道吸收率的可能性。评估4b的抗抑郁药和抗焦虑药活性表明，在相同剂量的1.25 mg / kg时，两种活性均具有特异性。4b的抗抑郁和/或抗焦虑特性可能与其首过效应有关。
• Structure–activity relationships and molecular studies of novel arylpiperazinylalkyl purine-2,4-diones and purine-2,4,8-triones with antidepressant and anxiolytic-like activity
  作者：Agnieszka Zagórska、Marcin Kołaczkowski、Adam Bucki、Agata Siwek、Grzegorz Kazek、Grzegorz Satała、Andrzej J. Bojarski、Anna Partyka、Anna Wesołowska、Maciej Pawłowski

  DOI：10.1016/j.ejmech.2015.04.046

  日期：2015.6

  A novel series of arylpiperazinylalkyl purine-2,4-diones (4-27) and purine-2,4,8-triones (31-38) was synthesized and tested to evaluated their affinity for the serotoninergic (5-HT1A, 5-HT6, 5-HT7) and dopaminergic (D2) receptors. Compounds with purine-2,4-dione nucleus generally had affinity values higher than the corresponding purine-2,4,8-trione compounds. A spectrum of receptor activities was observed for compounds with a substituent at the 7-position of the imidazo[2,1-f]purine-2,4-dione system and some potent 5-HT1A (18, 25), 5-HT7 (14) and mixed 5-HT1A/5-HT7 (8, 9) receptor ligands with additional affinity for dopamine D2 receptors (15) has been identified. Moreover, docking studies proved that a substituent at the 7-position of 1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine-2,4-dione could be essential for receptor affinity and selectivity, especially towards 5-HT1A and 5-HT7. The results of the preliminary pharmacological in vivo studies of selected derivatives of 1,3-dimethyl-(1H,8H)imidazo[2,1-f]purine-2,4-dione, including 9 as a potential anxiolytic, 8 and 15 as potential antidepressants, and 18 and 25 as potential antidepressant and anxiolytic agents. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Synthesis and preliminary pharmacological evaluation of imidazo[2,1-f]purine-2,4-dione derivatives
  作者：Agnieszka Zagórska、Sławomir Jurczyk、Maciej Pawłowski、Małgorzata Dybała、Gabriel Nowak、Ewa Tatarczyńska、Agnieszka Nikiforuk、Ewa Chojnacka-Wójcik

  DOI：10.1016/j.ejmech.2009.07.014

  日期：2009.11

  A series of N-8-arylpiperazinylpropyl derivatives of 1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine-2,4-dione (2-10) and amide derivatives of 1,3-dimethyl-6,7-dihydroimidazo[2,1-f]purine-2,4-(1H,3H)-dione-7-carboxylic acid (11-13) were synthesized. Compounds (2-10) evaluated in vitro were potent 5-HT1A receptor ligands. Preclinical studies indicated that 8-[3-(N4-phenyl)-piperazin-N1-yl-propyl]-1,3-dimethyl(1H,8H)-imidazo[2,1-f]purine-2,4-dione (2) exerts anxiolytic-like activity in the four-plate test in mice: however its effect was weaker, than that produced by Diazepam. This compound and 8-[3-(N4-2'-metoxyphenyl)-piperazin-N1-yl-propyl]-1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine-2,4-dione (3) behaved like antidepressants in the forced swimming test in mice; and their activity in that model was comparable with the effect of Imipramine. The obtained results suggested that the long-chain arylpiperazines (LCAPs) linked to tricyclic derivatives of the theophylline remain a worthy of future research for obtaining new derivatives with potential anxiolytic/antidepressant activity. (C) 2009 Elsevier Masson SAS. All rights reserved.
• Zagórska, Agnieszka; Czopek, Anna; Chłoń-Rzepa, Grażyna, Acta poloniae pharmaceutica, 2017, vol. 74, # 6, p. 1729 - 1738
  作者：Zagórska, Agnieszka、Czopek, Anna、Chłoń-Rzepa, Grażyna、Pawłowski, Maciej、Siwek, Agata、Bednarski, Marek、Zygmunt, Małgorzata、Sapa, Jacek

  DOI：——

  日期：——