1,2-二氢吡唑并[4,3-g]喹唑啉-5-酮 | 71785-46-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 1,2-二氢吡唑并[4,3-g]喹唑啉-5-酮
• 英文名称: 1,6-Dihydro-5H-pyrazolo<4,3-g>chinazolin-5-on
• 英文别名: 1H-pyrazolo<4,3-g>quinazolin-5(6H)-one；1H-pyrazolo<4,3-g>quinazolinone；pyrazolo<4,3-g>quinazolinone；lin-benzoallopurinol；1,6-dihydro-pyrazolo[4,3-g]quinazolin-5-one；lin-Benzoallopurinol；1,2-Dihydro-5H-pyrazolo[4,3-g]quinazolin-5-one；1,6-dihydropyrazolo[4,3-g]quinazolin-5-one
• CAS: 71785-46-1
• 化学式: C₉H₆N₄O
• 分子量: 186.173
• InChiKey: QNCOUBPRJGAMNN-UHFFFAOYSA-N

物化性质

• 熔点：
  >330 °C
• 沸点：
  488.5±37.0 °C(Predicted)
• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,2-二氢吡唑并[4,3-g]喹唑啉-5-酮 在 xanthine oxidase 作用下， 生成 1,8-Dihydro-5H-pyrazolo<4,3-g>chinazolin-5,7(6H)-dion
  参考文献：
  名称：

  Benzologs of allopurinol: Synthesis of pyrazolo [4,3-g] and [3,4-f] quinazolinones

  摘要：

  DOI：

  10.1016/s0040-4039(00)77398-9
• 作为产物：
  描述：

  6-氨基-5-甲基吲唑 在 盐酸 、 potassium permanganate 作用下， 以 水 、 溶剂黄146 、 叔丁醇 为溶剂， 反应 12.0h， 生成 1,2-二氢吡唑并[4,3-g]喹唑啉-5-酮
  参考文献：
  名称：

  核苷，39 1）角和线性二异嘌呤醇：吡唑并[4,3- f ]-和吡唑并[4,3-g]

  摘要：

  Ausgehend von 5-Aminoindazol （6） bzw。5-甲基-6-硝基吲哚（17），在3,8-Dihydro-9 H -pyrazolo [4,3- f ] chinazolin-9-on（3），einem gewinkelten Benzologen von Allopurinol（图1A），UND献给模具吡唑并[4,3-克] chinazolin -5-酮4，29，30 UND 31，模具gestreckt erweiterte Benzologe darstellen。4 UND 30维森EINE DEM的别嘌呤醇vergleichbare Hemmung DER黄嘌呤氧化酶AUF，wobei 4的Unten氧化的Zum 7-OX-衍生金融31 Auch als Substrat fungiert。

  DOI：

  10.1002/cber.19811140506

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
• Pyrazolo-quinazoline derivatives and methods of producing such derivatives
  申请人：SIEGFRIED AKTIENGESELLSCHAFT

  公开号：EP0040872A1

  公开（公告）日：1981-12-02

  Novel benzologs or pyrazolo-quinazoline derivatives of the formula (I) wherein X and Y are independently selected from oxygen, sulphur and imino and wherein ring (C) is a pyrazole ring fused to ring (B) via one of the three ortho-positions or sides of ring (B); the fused pyrazole ring (C) is either in the 4,3- or the 3,4-arrangement; and tautomers of formula (I) compounds; when X is not oxygen, i.e. stands for sulphur or imino, Y may stand for a covalent bond that links the hydrogen directly to the carbon atom in position 2.

  式(I)的新型苯并类化合物或吡唑-喹唑啉衍生物 其中 X 和 Y 独立选自氧、硫和亚氨基，且环 (C) 是通过环 (B) 的三个正交位置或侧面之一与环 (B) 融合的吡唑环；融合的吡唑环 (C) 为 4,3- 或 3,4- 排列；以及式 (I) 化合物的同系物；当 X 不是氧，即代表硫或亚氨基时，Y 可代表将氢直接与碳相连的共价键。当 X 不是氧时，即代表硫或亚氨基时，Y 可代表将氢直接连接到第 2 位碳原子的共价键。
• Benzologs of allopurinol: Synthesis of pyrazolo [4,3-g] and [3,4-f] quinazolinones
  作者：Eckehard Cuny、F.W. Lichtenthaler、Alfred Moser

  DOI：10.1016/s0040-4039(00)77398-9

  日期：1980.1
• Tyrosine Kinase Inhibitors. 11. Soluble Analogues of Pyrrolo- and Pyrazoloquinazolines as Epidermal Growth Factor Receptor Inhibitors:  Synthesis, Biological Evaluation, and Modeling of the Mode of Binding
  作者：Brian D. Palmer、Susanne Trumpp-Kallmeyer、David W. Fry、James M. Nelson、H. D. Hollis Showalter、William A. Denny

  DOI：10.1021/jm960789h

  日期：1997.5.1

  A new route to N-1-substituted pyrazolo- and pyrroloquinazolines has been developed from the known quinazolones 19 and 23, via conversion to the corresponding thiones, S-methylation to the thioethers, N-1-alkylation, and coupling with 3-bromoaniline. C-S-Substituted pyrroloquinazolines were prepared by Mannich base chemistry. A series of compounds bearing solubilizing side chains at these positions has been prepared and evaluated for inhibition of the tyrosine kinase activity of the isolated epidermal growth factor receptor (EGFR) and of its autophosphorylation in EGF-stimulated A431 cells. Several analogues, particularly C-3-substituted pyrroloquinazolines, retained high potency in both assays. A model for the binding of the general class of 4-anilinoquinazolines to the EGFR was constructed from structural information (particularly for the catalytic subunit of the cAMP-dependent protein kinase) and structure-activity relationships (SAR) in the series. In this model, the pyrrole ring in pyrroloquinazolines (and the 6- and 7-positions of quinazoline and related pyridopyrimidine inhibitors) occupies the entrance of the ATP binding pocket of the enzyme, with the pyrrole nitrogen located at the bottom of the cleft and the pyrrole C-3 position pointing toward a pocket corresponding to the ribose binding site of ATP. This allows considerable bulk tolerance for C-3 substituents and lesser but still significant bulk tolerance for N-1 substituents. The observed high selectivity of these compounds for binding to EGFR over other similar tyrosine kinases is attributed to the 4-anilino ring binding in an adjacent hydrophobic pocket which has an amino acid composition unique to the EGFR. The SAR seen for inhibition of the isolated enzyme by the pyrazolo- and pyrroloquinazolines discussed here is fully consistent with this binding model. For the N-1-substituted compounds, inhibition of autophosphorylation in A431 cells correlates well with inhibition of the isolated enzyme, as seen previously for related pyridopyrimidines. However, the C-S-substituted pyrroloquinazolines show unexpectedly high potencies in the autophosphorylation assay, making them of particular interest.
• CUNY E.; LICHTENTHALER F. W.; MOSER A., TETRAHEDRON LETT., 1980, 21, NO 32, 3029-3032
  作者：CUNY E.、 LICHTENTHALER F. W.、 MOSER A.

  DOI：——

  日期：——