7-(2-bromoethyl)-8-bromotheophylline | 58431-80-4

• 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-(2-bromoethyl)-8-bromotheophylline
• 英文别名: 7-β-bromoethyl-8-bromotheophylline；8-bromo-7-(2-bromoethyl)theophylline；8-bromo-7-(2-bromoethyl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione；7--8-bromtheophyllin；8-bromo-7-(2-bromo-ethyl)-1,3-dimethyl-3,7-dihydro-purine-2,6-dione；8-Brom-7-(2-brom-aethyl)-1,3-dimethyl-3,7-dihydro-purin-2,6-dion；8-bromo-7-(2-bromoethyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione；8-bromo-7-(2-bromoethyl)-1,3-dimethylpurine-2,6-dione
• CAS: 58431-80-4
• 化学式: C₉H₁₀Br₂N₄O₂
• 分子量: 366.012
• InChiKey: YWTIGWWOLSQHAJ-UHFFFAOYSA-N

物化性质

• 熔点：
  160-162 °C
• 沸点：
  494.6±55.0 °C(Predicted)
• 密度：
  2.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  58.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-(2-bromoethyl)-8-bromotheophylline 在 sodium sulfide 作用下， 生成 1,3-dimethyl-6,7-dihydro[1,3]thiazolo[2,3-f]purine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Cacace; Masironi, Annali di Chimica, 1956, vol. 46, p. 806,808

  摘要：

  DOI：
• 作为产物：
  描述：

  茶碱 在 sodium chlorate 、 苄基三乙基氯化铵 、 氢溴酸 、 potassium carbonate 、 溶剂黄146 作用下， 以 丙酮 为溶剂， 生成 7-(2-bromoethyl)-8-bromotheophylline
  参考文献：
  名称：

  三环环烷基咪唑基，嘧啶基和二氮杂pin啶二酮的合成及生物活性

  摘要：

  描述了N-环烷基取代的咪唑基，嘧啶基和1,3-二氮杂[ 2,1 - f ]嘌呤二酮的合成及其理化性质。这些衍生物是通过7-卤代烷基-8-溴-1,3-二甲基黄嘌呤衍生物与氨基环烷烃的环化反应合成的。将所得到的化合物（1 - 33），用于他们的大鼠腺苷A亲和评价1和A 2A受体。另外研究了所选化合物对人A 1，A 2A，A 2B和A 3受体亚型的亲和力。腺苷A 1和A 2A的放射性配体结合测定结果受体显示，大多数化合物在微摩尔或亚微摩尔浓度下均表现出腺苷A 2A受体亲和力。退火的嘧啶环对于A 2A亲和力是有益的。本系列中最有效的A 2A配体是化合物6（K i 0.33μM大鼠A 2A，0.31μM人A 2A），8（K i 0.98μM大鼠A 2A，0.42μM人A 2A）和15（K i 0.24μM大鼠A 2A，0.61μM人类A 2A），后者显示出较高的A 2A选择性。在NaCl位移分析中，显示15是A

  DOI：

  10.1016/j.ejmech.2011.05.023

文献信息

• Novel multi-target directed ligands based on annelated xanthine scaffold with aromatic substituents acting on adenosine receptor and monoamine oxidase B. Synthesis, in vitro and in silico studies
  作者：Michał Załuski、Jakub Schabikowski、Miriam Schlenk、Agnieszka Olejarz-Maciej、Bartłomiej Kubas、Tadeusz Karcz、Kamil Kuder、Gniewomir Latacz、Małgorzata Zygmunt、David Synak、Sonja Hinz、Christa E. Müller、Katarzyna Kieć-Kononowicz

  DOI：10.1016/j.bmc.2019.02.004

  日期：2019.4

  dual-target-directed ligands combining A2A adenosine receptor (AR) antagonistic activity with blockade of monoamine oxidase B (MAO-B). A library of 37 novel compounds was synthesized and biologically evaluated in radioligand binding studies at AR subtypes and for their ability to inhibit MAO-B. A systematic modification of the tricyclic structures based on a xanthine core by enlargement of the third heterocyclic

  N9-苄基取代的咪唑基-，嘧啶基-和1,3-二氮杂[2,1-f]嘌呤二酮被设计为双靶标配体，结合了A2A腺苷受体（AR）拮抗活性和单胺氧化酶B（MAO）的阻断作用-B）。合成了37种新化合物的文库，并通过放射性配体结合研究对AR亚型及其抑制MAO-B的能力进行了生物学评估。基于黄嘌呤核的三环结构的系统修饰通过扩大第三杂环或连接各种取代的苄基部分而导致开发了9-（2-氯-6-氟苄基）-1,3-二甲基-6 ，7,8,9-四氢嘧啶基[2,1-f]嘌呤-2,4（1H，3H）-二酮（9u; Ki人A2AAR：189 nM和IC50人MAO-B：570 nM）是最有效的该系列的双作用配体相对于相关靶标显示出高选择性。此外，在嘧啶基和1，3-二氮杂p [2，1-f]嘌呤二酮类中鉴定出一些有效的，选择性的MAO-B抑制剂。化合物10d（10-（3,4-二氯苄基）-1,3-二甲基-7,8,9,10-四氢-1H-
• Discovery of Tricyclic Xanthines as Agonists of the Cannabinoid-Activated Orphan G-Protein-Coupled Receptor GPR18
  作者：Clara T. Schoeder、Andhika B. Mahardhika、Anna Drabczyńska、Katarzyna Kieć-Kononowicz、Christa E. Müller

  DOI：10.1021/acsmedchemlett.0c00208

  日期：2020.10.8

  GPR18 is a rhodopsin-like orphan G-protein-coupled receptor (GPCR) that is activated by the natural cannabinoid (CB) Δ9-tetrahydrocannabinol (THC). It is highly expressed in immune cells and represents a promising new drug target. However, THC is much more potent in activating CB receptors than GPR18, and several other proposed lipidic agonists for GPR18 have not been independently confirmed. Herein

  GPR18 是一种视紫质样孤儿 G 蛋白偶联受体 (GPCR)，由天然大麻素 (CB) Δ 9 -四氢大麻酚 (THC)激活。它在免疫细胞中高度表达，代表了一个有前途的新药物靶点。然而，THC 在激活 CB 受体方面比 GPR18 更有效，并且其他几种提议的 GPR18 脂质激动剂尚未得到独立证实。在此，我们描述了第一个基于三环黄嘌呤衍生支架的 GPR18 非脂质样激动剂，以及初始结构-活性关系。PSB-KD107 ( 5 ) 和 PSB-KD477 ( 16) 显示出比 THC 显着更高的效力和功效，在 GPR18 依赖性 β-抑制蛋白募集试验中确定，并且被发现对 CB 敏感受体 CB 1、CB 2和 GPR55 具有选择性。构效关系陡峭，吲哚取代对生物活性至关重要。这些第一个选择性激动剂在结构上与脂质激动剂不同，将允许进行目标验证研究，并可能最终有助于 GPR18 的脱孤。
• Synthesis and CNS activity of tricyclic theophylline derivatives. 8-substituted imidazo[2,1-f]theophyllines
  作者：Maciej Pawłowski、Anna Drabczyńska、Jacek Katlabi、Maria Gorczyca、Danuta Malec、Jerzy Modzelewski

  DOI：10.1016/s0223-5234(99)00131-2

  日期：1999.12

  Based on previously described results of pharmacological in vitro and in vivo tests of some series of pyrimido- and diazepino-[2,1-f]theophylline derivatives, Ns-unsubstituted, N8-benzyl and N8-arylpiperazino-alkyl derivatives of imidazo[2,1-f]theophyllines were synthesized and tested for their CNS activity. It has been shown that tricyclic [2,1-f]theophyllines possess sedative and analgesic activity. N8-Phenylpiperazinopropyl-1,3,6,7-tetrahydro-(8H)-imidazo[2,1-f]theophylline 6 showed significant anti-serotonin and long-lasting hypothermic effects. N8-Benzyl-1,3,6,8-tetrahydroimidazo-7-on[2,1-f]theophylline 8 possess anticonvulsant properties. (C) 1999 Editions scientifiques et medicales Elsevier SAS.
• Synthesis and biological activity of tricyclic aryloimidazo-, pyrimido-, and diazepinopurinediones
  作者：Anna Drabczyńska、Christa E. Müller、Svenja K. Lacher、Britta Schumacher、Janina Karolak-Wojciechowska、Antony Nasal、Piotr Kawczak、Olga Yuzlenko、Elżbieta Pękala、Katarzyna Kieć-Kononowicz

  DOI：10.1016/j.bmc.2006.06.052

  日期：2006.11

  Syntheses and physicochemical properties of N-aryl-substituted imidazo-, pyrimido-, and 1,3-diazepino[2,1-f]purinediones are described. These derivatives were synthesized by the cyclization of 7-haloalkyl-8-bromo-1,3-dimethyl- or 1,3-dipropyl-xanthine derivatives with corresponding arylamines. The obtained compounds (1-40), which can be envisaged as sterically fixed and configurationally stable analogs of 8-styrylxanthines, were evaluated for their affinity to adenosine A(1) and A(2A) receptors, the receptor subtypes that are predominant in the brain. Selected compounds were additionally investigated for affinity to the A(2B) and A(3) receptor subtypes. Many of the compounds showed adenosine A(2A) receptor affinity at micromolar or submicromolar concentrations and were A(2A)-selective, for example, compound 23 with p-fluoro substituent displayed K-i value of 0.147 mu M at the rat A2A receptor and more than 170-fold-A(2A) selectivity, compound 17 with naphthyl substituent had K-i value of 0.219 mu M and a more than 114-fold-A2A selectivity. The compounds were-somewhat weaker and less selective at the human receptor subtypes. Elongation of the dimethyl substituent to dipropyl in xanthine moiety improved affinity but reduced selectivity. 1,3-Dimethylimidazo-, pyrimido-, and diazepinopurinediones were evaluated in vivo as anticonvulsants in MES, ScMet, TTE tests and examined for neurotoxicity in mice (ip). Substances with pyrimido ring displayed protective activity in ScMet or in MES and ScMet tests, showing also neurotoxicity. The pyrimidine annelated ring is beneficial for both receptor affinity and anticonvulsant activity. (c) 2006 Elsevier Ltd. All rights reserved.
• TSALMANE, L. V.;LIDAK, M. YU., BIOORGAN. XIMIYA, 16,(1990) N, S. 976-980
  作者：TSALMANE, L. V.、LIDAK, M. YU.

  DOI：——

  日期：——