2-methylbenzo[g]quinazolin-4(3H)-one | 16673-88-4

• 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: 2-methylbenzo[g]quinazolin-4(3H)-one
• 英文别名: 2-Methylbenzo[g]quinazolin-4(3H)-one；2-methyl-3H-benzo[g]quinazolin-4-one
• CAS: 16673-88-4
• 化学式: C₁₃H₁₀N₂O
• 分子量: 210.235
• InChiKey: CYCCTYUWQCTYGY-UHFFFAOYSA-N

物化性质

• 熔点：
  320 °C
• 沸点：
  412.7±28.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-methylbenzo[g]quinazolin-4(3H)-one 在 硫酸 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 90.0~190.0 ℃ 、700.01 kPa 条件下， 反应 13.5h， 生成 (E)-4-chloro-2-(4-chlorostyryl)benzo[g]quinazoline
  参考文献：
  名称：

  发现和开发ITD和D835Y突变FLT3激酶的极端选择性抑制剂。

  摘要：

  FMS样酪氨酸受体激酶3（FLT3）的异常激活与20-30％的患者的急性髓细胞性白血病（AML）的发病机制有关。在这项研究中，我们确定了高选择性（苯基乙烯基）喹唑啉化合物家族作为FLT3-ITD和FLT3-D835Y激酶的新型有效抑制剂。通过生化和细胞增殖测定以及随后的小鼠异种移植研究，证实了它们的显着效果。我们的建模实验和化合物的化学结构预测了共价抑制的可能性。最有效的化合物触发了FLT3-ITD AML细胞的凋亡，但在不依赖FLT3的白血病和非白血病细胞系中作用微弱或没有作用。

  DOI：

  10.1016/j.ejmech.2019.111710
• 作为产物：
  描述：

  3-(乙酰氨基)-2-萘甲酸 在 氨 、 水 作用下， 反应 12.0h， 生成 2-methylbenzo[g]quinazolin-4(3H)-one
  参考文献：
  名称：

  喹唑啉作为细菌细胞分裂蛋白 FtsZ 抑制剂的合成和评价。

  摘要：

  细菌细胞分裂蛋白 FtsZ 是开发新型抗生素的众多潜在目标之一。最近，zantrin Z3 被证明是 FtsZ 的跨物种抑制剂；然而，它与蛋白质的特定相互作用仍然未知。在此，我们报告了包含更易处理的核心结构的类似物的合成，以及对 FtsZ 的 GTPase 活性具有个位数微摩尔抑制的类似物，这是迄今为止报道的最有效的大肠杆菌FtsZ抑制剂。此外，zantrin Z3 核心已转化为两种潜在的光交联试剂，用于蛋白质组学研究，可以阐明 FtsZ 与与 zantrin Z3 相关的分子之间的分子相互作用。

  DOI：

  10.1021/ml500497s

文献信息

• [EN] STYRYL QUINAZOLINE DERIVATIVES AS PHARMACEUTICALLY ACTIVE AGENTS<br/>[FR] DÉRIVÉS STYRYL QUINAZOLINE UTILISÉS COMME AGENTS PHARMACEUTIQUEMENT ACTIFS
  申请人：VICHEM CHEMIE KUTATÓ KFT

  公开号：WO2015019121A1

  公开（公告）日：2015-02-12

  The present invention relates to styryl quinazoline derivatives of the general formula (I) and pharmaceutically acceptable solvates, hydrates, salts, regioisomeric and polymorphic forms thereof as well as pharmaceutical compositions containing at least one of the described compounds as pharmaceutically active agent. The compounds have been identified as new drug candidates for the prevention and/or treatment of diseases related to disfunction(s) of hematopoiesis and cancer or any other form of neo- or hyperplasias related to Fms-like tyrosine kinase 3 (FLT3) containing Internal Tandem Duplications (ITD), especially in the case of myeloid leukemia. The compounds have been also identified as new drug candidates as antibacterial agents (having bactericidal or bacteriostatic activity) which can be used for the prevention and/or treatment of bacterial infectious diseases. ˙

  本发明涉及通式（I）的芳基喹唑啉衍生物以及药学上可接受的溶剂化合物、水合物、盐、异构体和多晶形式，以及包含至少一种所述化合物作为药学活性剂的药物组合物。这些化合物已被确认为预防和/或治疗与造血功能异常和癌症或与含有内部串联重复（ITD）的Fms样酪氨酸激酶3（FLT3）相关的疾病有关的新药候选化合物，特别是在髓样白血病的情况下。这些化合物还被确认为新的抗菌剂候选药物（具有杀菌或抑菌活性），可用于预防和/或治疗细菌感染性疾病。
• [EN] ANTIBIOTICS EFFECTIVE FOR GRAM-NEGATIVE PATHOGENS<br/>[FR] ANTIBIOTIQUES EFFICACES CONTRE LES PATHOGÈNES GRAM-NÉGATIFS
  申请人：UNIV ILLINOIS

  公开号：WO2019177975A1

  公开（公告）日：2019-09-19

  Disclosed herein are antibacterial compounds that accumulate in Gram-negative bacteria, methods of preparing the compounds, and methods of using the compounds to inhibit or kill microbes, and methods of treating microbial infections, such as Gram-negative bacterial infections. Compounds selected for conversion to potential Gram-negative antibacterial compounds were identified based on compounds having low globularity and low flexibility. Amine substituents were then strategically added to the selected compounds to provide compounds having antibacterial activity against Gram-negative bacteria.

  本文披露了在革兰氏阴性细菌中积累的抗菌化合物，制备这些化合物的方法，以及利用这些化合物抑制或杀灭微生物，以及治疗微生物感染的方法，如革兰氏阴性细菌感染。选择用于转化为潜在革兰氏阴性抗菌化合物的化合物是基于具有低球形度和低柔性的化合物。然后在所选的化合物中策略性地添加氨基取代基，以提供对革兰氏阴性细菌具有抗菌活性的化合物。
• STYRYL QUINAZOLINE DERIVATIVES AS PHARMACEUTICALLY ACTIVE AGENTS
  申请人：VICHEM CHEMIE KUTATÓ KFT.

  公开号：US20160194291A1

  公开（公告）日：2016-07-07

  The present invention relates to styryl quinazoline derivatives of the general formula (I) and pharmaceutically acceptable solvates, hydrates, salts, regioisomeric and polymorphic forms thereof as well as pharmaceutical compositions containing at least one of the described compounds as pharmaceutically active agent. The compounds have been identified as new drug candidates for the prevention and/or treatment of diseases related to disfunction(s) of hematopoiesis and cancer or any other form of neo- or hyperplasias related to Fms-like tyrosine kinase 3 (FLT3) containing Internal Tandem Duplications (ITD), especially in the case of myeloid leukemia. The compounds have been also identified as new drug candidates as antibacterial agents (having bactericidal or bacteriostatic activity) which can be used for the prevention and/or treatment of bacterial infectious diseases.

  本发明涉及一般式（I）的苯乙烯基喹唑啉衍生物及其药学上可接受的溶剂化物、水合物、盐、区域异构体和多晶形式，以及包含所述化合物中至少一种作为药学活性剂的制药组合物。这些化合物已被确定为新药候选物，用于预防和/或治疗与造血功能障碍和癌症或与含有内部串联重复（ITD）的Fms样酪氨酸激酶3（FLT3）相关的任何形式的新生或增生有关的疾病，特别是髓系白血病的情况。这些化合物还被确定为新的抗菌剂（具有杀菌或抑菌活性），可用于预防和/或治疗细菌感染性疾病。
• Etienne; Legrand, Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1949, vol. 229, p. 220
  作者：Etienne、Legrand

  DOI：——

  日期：——
• Comparison of Small Molecule Inhibitors of the Bacterial Cell Division Protein FtsZ and Identification of a Reliable Cross-Species Inhibitor
  作者：David E. Anderson、Michelle B. Kim、Jared T. Moore、Terrence E. O’Brien、Nohemy A. Sorto、Charles I. Grove、Laura L. Lackner、James B. Ames、Jared T. Shaw

  DOI：10.1021/cb300340j

  日期：2012.11.16

  ZFtsZ is a guanosine triphosphatase (GTPase) that mediates cytokinesis in bacteria. FtsZ is homologous in structure to eukaryotic tubulin and polymerizes in a similar head-to-tail fashion. The study of tubulin's function in eukaryotic cells has benefited greatly from specific and potent small molecule inhibitors, including colchicine and taxol. Although many small molecule inhibitors of FtsZ have been reported, none has emerged as a generally useful probe for Modulating bacterial cell division. With the goal of establishing a useful and reliable small molecule inhibitor of FtsZ, a broad biochemical cross comparison of reported FtsZ, inhibitors was undertaken. Several of these molecules, including phenolic natural products, are unselective inhibitors that seem to;derive their activity from the formation of microscopic colloids or aggregates. Other compounds, including the natural product viriditoxin and the drug development candidate PC190723, exhibit no inhibition of GTPase activity Using protocols in this work or under published conditions. Of the compounds studied, only zantrin Z3 exhibits good levels of inhibition, maintains activity under conditions that disrupt small molecule aggregates, and provides a platform for exploration of structure-activity relationships (SAR). Preliminary SAR studies have identified slight modifications to the two side chains of this structure that modulate the inhibitory activity of zantrin Z3. Collectively, these studies will help focus future investigations toward the establishment of probes for FtsZ that fill the roles of colchicine and taxol in studies of tubulin.