8-(methylthio)-1H-imidazo<4,5-g>quinazoline | 53449-20-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 8-(methylthio)-1H-imidazo<4,5-g>quinazoline
• 英文别名: 4-methylthio-6H-imidazo[4,5-g]quinazoline；8-(Methylsulfanyl)-1H-imidazo[4,5-g]quinazoline；8-methylsulfanyl-1H-imidazo[4,5-g]quinazoline
• CAS: 53449-20-0
• 化学式: C₁₀H₈N₄S
• 分子量: 216.266
• InChiKey: AFFAOBKYROOVHB-UHFFFAOYSA-N

物化性质

• 沸点：
  556.3±30.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  79.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-(methylthio)-1H-imidazo<4,5-g>quinazoline 在 18-冠醚-6 、 磷酸三乙酯 、 氨 、 potassium carbonate 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 生成 Phosphoric acid mono-[(2S,4S)-4-(8-amino-imidazo[4,5-g]quinazolin-3-yl)-tetrahydro-furan-2-ylmethyl] ester
  参考文献：
  名称：

  Inhibition of HIV integrase by novel nucleotides bearing tricyclic bases

  摘要：

  5'-Monophosphates of several novel dideoxynucleosides bearing tricyclic nucleobases were synthesized. Both linear and angular ring-extended analogs of isomeric dideoxyadenosine 5'-monophosphate were discovered to have moderate to good inhibition of the viral-encoded enzyme, HIV integrase. The results suggest that the nucleotide binding site of HIV integrase can accommodate major modifications in the nucleobase, which is in stark contrast to the nucleotide binding site on HIV reverse transcriptase, (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00327-8
• 作为产物：
  描述：

  5,6-二甲基苯并咪唑 在 吡啶 、 氢氧化钾 、 potassium permanganate 、 tetraphosphorus decasulfide 、 叠氮基三甲基硅烷 作用下， 以 叔丁醇 为溶剂， 反应 47.5h， 生成 8-(methylthio)-1H-imidazo<4,5-g>quinazoline
  参考文献：
  名称：

  Toward a New Genetic System with Expanded Dimensions:  Size-Expanded Analogues of Deoxyadenosine and Thymidine

  摘要：

  We describe the design, preparation, and properties of two key building blocks of a size-expanded genetic system. Nucleoside analogues of the natural nucleosides dA and dT are reported in which the fusion of a benzo ring increases their size by ca. 2.4 Angstrom. The expanded dA analogue (dxA), having a tricyclic base, was first reported by Leonard nearly three decades ago. We describe a shortened and more efficient approach to this compound. The expanded dT analogue (dxT), a methylquinazolinedione C-glycoside, was previously unknown; we describe its preparation in eight steps from 5-methylanthranilic acid. The key glycoside bond formation employed Pd-mediated coupling of an aryl iodide precursor with a dihydrofuran derivative of deoxyribose. Both nucleosides are shown to be efficient fluorophores, emitting light in the blue-violet range. The base-protected phosphoramidite derivatives were prepared, and short oligonucleotides containing them were characterized. The two size-expanded nuclecisides are key components of a new four-base genetic system designed to form helical paired structures having a diameter greater than that of natural DNA. Elements of the design of this expanded genetic molecule, termed xDNA, are discussed, including the possibility of up to eight base pairs of information storage capability.

  DOI：

  10.1021/ja038384r

文献信息

• Tyrosine Kinase Inhibitors. 9. Synthesis and Evaluation of Fused Tricyclic Quinazoline Analogues as ATP Site Inhibitors of the Tyrosine Kinase Activity of the Epidermal Growth Factor Receptor
  作者：Gordon W. Rewcastle、Brian D. Palmer、Alexander J. Bridges、H. D. Hollis Showalter、Li Sun、James Nelson、Amy McMichael、Alan J. Kraker、David W. Fry、William A. Denny

  DOI：10.1021/jm950692f

  日期：1996.1.1

  4-[(3-bromophenyl)amino]-6,7-dimethoxyquinazoline (4; PD 153035) as an extremely potent (IC(50) 0.025 nM) inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), several fused tricyclic quinazoline analogues have been prepared and evaluated for their ability to inhibit the enzyme. The most potent compound was the linear imidazo[4,5-g]quinazoline (8), which exhibited an IC(50) of 0

  发现4-[（（3-溴苯基）氨基] -6,7-二甲氧基喹唑啉（4; PD 153035）作为表皮生长因子受体酪氨酸激酶活性的极强抑制剂（IC（50）0.025 nM） （EGFR），已经制备了几种稠合的三环喹唑啉类似物，并对其抑制酶的能力进行了评估。最有效的化合物是线性咪唑并[4,5-g]喹唑啉（8），其IC（50）为0.008 nM，可抑制磷脂酶C-gamma-1片段作为底物的磷酸化。虽然8的N-甲基类似物显示出相似的效价，但类似的N- [2-（二甲基氨基）乙基]衍生物效果较差。接下来最有效的化合物是线性吡唑并喹唑啉（19和20）（IC（50）s为0.34和0.44 nM）和吡咯并喹唑啉（21）（IC（50）为0.44nM），而其他几个几何形状类似于8的线性三环系统（三唑并，噻唑并和吡嗪并喹唑啉）的效果则较差。在咪唑并[4,5-g]喹唑啉和吡咯并喹唑啉系列中，相应的角型异构体的效力也远低于
• Phenylamino-substituted tricyclic derivatives for treatment of hyperproliferative diseases
  申请人：Pfizer Inc.

  公开号：US06335344B1

  公开（公告）日：2002-01-01

  The present invention relates to compounds of the formula (I) and to pharmaceutically acceptable salts thereof, wherein R1-R4 and Z are as defined herein. The compounds of formula (I) are useful as antiproliferative agents. The invention further relates to pharmaceutical compositions and methods of treating hyperproliferative disorders such as cancer, using such compounds.

  本发明涉及式（I）化合物及其药学上可接受的盐，其中R1-R4和Z的定义如本文所述。式（I）化合物可用作抗增殖剂。本发明还涉及药物组合物和使用这些化合物治疗高增殖性疾病（如癌症）的方法。
• Quinazoline Derivatives and Therapeutic Use Thereof
  申请人：Lee Young B.

  公开号：US20090030021A1

  公开（公告）日：2009-01-29

  Quinazoline derivatives represented by the general formula pharmacologically acceptable salts thereof, and compositions containing such compounds are described. Methods for using the compounds for treatment of hyperproliferative disorders are also disclosed.

  本发明涉及一般式所代表的喹唑啉衍生物，其药物学上可接受的盐以及含有这些化合物的组合物。还公开了使用这些化合物治疗过度增殖性疾病的方法。
• Quinazoline derivatives and therapeutic use thereof
  申请人：Rexahn Pharmaceuticals, Inc.

  公开号：EP2650286A1

  公开（公告）日：2013-10-16

  Quinazoline derivatives represented by the general formula, pharmacologically acceptable salts thereof, and compositions containing such compounds are described. Methods for using the compounds for treatment of hyperproliferative disorders are also disclosed.

  本文描述了通式所代表的喹唑啉衍生物、其药理学上可接受的盐类以及含有此类化合物的组合物。还公开了使用这些化合物治疗过度增殖性疾病的方法。
• Synthesis of New Dideoxynucleosides Bearing Ring-Extended Nucleobases
  作者：Jianzhong Zhang、Vasu Nair

  DOI：10.1080/07328319708006139

  日期：1997.7

  New dideoxynucleosides where the nucleobase is lin-benzoadenine is reported. The key target compound, (S, S)-isodideoxybenzoadenosine, is stable with respect to hydrolytic cleavage of the glycosyl bond and it is a poor substrate for adenosine deaminase. Its monophosphate is not a substrate for AMP deaminase.