7-acetonyl-8-bromotheophylline | 19977-31-2

• 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: 7-acetonyl-8-bromotheophylline
• 英文别名: 8-bromo-1,3-dimethyl-7-(2-oxopropyl)-3,7-dihydro-1H-purine-2,6-dione；8-acetonyl-8-bromotheophylline；7-Acetylmethyl-8-brom-theophyllin；8-Brom-7-acetonyl-theophyllin；8-bromo-1,3-dimethyl-7-(2-oxo-propyl)-3,7-dihydro-purine-2,6-dione；7-acetonyl-8-bromo-1,3-dimethyl-3,7-dihydro-purine-2,6-dione；7-Acetonyl-8-brom-1,3-dimethyl-3,7-dihydro-purin-2,6-dion；8-bromo-1,3-dimethyl-7-(2-oxopropyl)purine-2,6-dione
• CAS: 19977-31-2
• 化学式: C₁₀H₁₁BrN₄O₃
• 分子量: 315.126
• InChiKey: ZZTWXVKYKRBBRD-UHFFFAOYSA-N

物化性质

• 熔点：
  203 °C
• 沸点：
  493.8±55.0 °C(Predicted)
• 密度：
  1.79±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 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：

  7-acetonyl-8-bromotheophylline 在 一水合肼 作用下， 生成 3,7,9-trimethyl-1,4-dihydro-9H-[1,2,4]triazino[3,4-f]purine-6,8-dione
  参考文献：
  名称：

  Zelnick et al., Bulletin de la Societe Chimique de France, 1956, p. 888,892

  摘要：

  DOI：
• 作为产物：
  描述：

  8-溴茶碱 以75%的产率得到
  参考文献：
  名称：

  KRASOVSKIJ A. N.; YURCHENKO M. I.; KOCHERGIN P. M.; COPOKA I. I., XIMIYA GETEROTSIKL. SOEDIN. , 1975, HO 8, 1121-1123

  摘要：

  DOI：

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。
• Synthesis and Physicochemical Properties of Imidazo[1,2-f]Xanthine Derivatives
  作者：N. I. Romanenko、T. N. Rak、O. A. Pakhomova、D. G. Ivanchenko、A. A. Mylova

  DOI：10.1007/s10600-014-0871-6

  日期：2014.3

  A simple preparative method for the synthesis of imidazo[1,2-f]xanthine derivatives, promising synthons for further modification of the xanthine molecule, was developed. The spectral characteristics of the synthesized compounds were studied.

  研究人员开发了一种合成咪唑并[1,2-f]黄嘌呤衍生物的简单制备方法，这种衍生物有望进一步修饰黄嘌呤分子。研究了合成化合物的光谱特征。
• 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
  作者：Agnieszka Zagórska、Anna Czopek、Maciej Pawłowski、Małgorzata Dybała、Agata Siwek、Gabriel Nowak

  DOI：10.1007/s00044-011-9883-y

  日期：2012.11

  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.
• 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.