ethyl 6-bromo-4-oxo-3,4-dihydroquinazoline-2-carboxylate | 926273-65-6

• 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: ethyl 6-bromo-4-oxo-3,4-dihydroquinazoline-2-carboxylate
• 英文别名: ethyl 6-bromo-4-oxo-3H-quinazoline-2-carboxylate
• CAS: 926273-65-6
• 化学式: C₁₁H₉BrN₂O₃
• mdl: MFCD09042597
• 分子量: 297.108
• InChiKey: FBXFISPUBFVIJK-UHFFFAOYSA-N

物化性质

• 沸点：
  423.2±47.0 °C(Predicted)
• 密度：
  1.69±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  67.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 6-bromo-4-oxo-3,4-dihydroquinazoline-2-carboxylate 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 水 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.5h， 生成 4-((3-chlorobenzyl)amino)-6-(3,5-dimethylisoxazol-4-yl)-N-(tetrahydro-2H-pyran-4-yl)quinazoline-2-carboxamide
  参考文献：
  名称：

  Discovery and lead identification of quinazoline-based BRD4 inhibitors

  摘要：

  A new series of quinazoline-based analogs as potent bromodomain-containing protein 4 (BRD4) inhibitors is described. The structure-activity relationships on 2- and 4-position of quinazoline ring, and the substitution at 6-position that mimic the acetylated lysine are discussed. A co-crystallized structure of 48 (CN750) with BRD4 (BD1) including key inhibitor-protein interactions is also highlighted. Together with preliminary rodent pharmacokinetic results, a new lead (65, CN427) is identified which is suitable for further lead optimization.

  DOI：

  10.1016/j.bmcl.2018.08.039
• 作为产物：
  描述：

  氰基甲酸乙酯 、 2-氨基-5-溴苯甲酸 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 生成 ethyl 6-bromo-4-oxo-3,4-dihydroquinazoline-2-carboxylate
  参考文献：
  名称：

  [EN] ISOINDOLINONE COMPOUNDS AS GPR119 MODULATORS FOR THE TREATMENT OF DIABETES, OBESITY, DYSLIPIDEMIA AND RELATED DISORDERS
  [FR] COMPOSÉS D'ISOINDOLINONE UTILISÉS COMME MODULATEURS DE GPR119 POUR LE TRAITEMENT DU DIABÈTE, DE L'OBÉSITÉ ET DE TROUBLES ASSOCIÉS

  摘要：

  本发明涉及异吲哚啉酮化合物。这些异吲哚啉酮化合物是GPR119调节剂，可用于预防和/或治疗糖尿病、肥胖、血脂异常和相关疾病。此外，本发明还涉及将异吲哚啉酮化合物用作药物的活性成分，以及包含它们的药物组合物。

  公开号：

  WO2015150565A1

文献信息

• [EN] BICYCLIC BET BROMODOMAIN INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE BROMODOMAINES BET BICYCLIQUES ET LEURS UTILISATIONS
  申请人：STROVEL JEFFREY WILLIAM

  公开号：WO2017091661A1

  公开（公告）日：2017-06-01

  The present invention relates to compounds that bind to and otherwise modulate the activity of bromodomain-containing proteins, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders.

  本发明涉及结合并调节含有溴结构域蛋白的化合物，制备这些化合物的方法，含有这些化合物的药物组合物，以及使用这些化合物治疗各种疾病和疾病的方法。
• A-ring and E-ring modifications of the cytotoxic alkaloid Luotonin A: Synthesis, computational and biological studies
  作者：Amra Ibric、Verena Battisti、Sophie Deckardt、Anna Veronika Haller、Calvin Lee、Corinna Prötsch、Thierry Langer、Petra Heffeter、Hemma Henrike Schueffl、Brigitte Marian、Norbert Haider

  DOI：10.1016/j.bmc.2020.115443

  日期：2020.5

  A series of new Luotonin A derivatives with substituents at rings A and E was synthesized, together with some E-ring-unsubstituted derivatives. Subsequently, the compound library was examined in silico for their binding into a previously proposed site in the DNA/topoisomerase I binary complex. Whereas no convincing correlation between docking scores and biological data from in vitro assays could be

  合成了一系列在环A和E上具有取代基的新的褪黑素A衍生物，以及一些未被E环取代的衍生物。随后，对该化合物文库进行计算机分析，以检查其与DNA /拓扑异构酶I二元复合物中先前提议的位点的结合。尽管没有发现对接分数与来自体外测定的生物学数据之间令人信服的相关性，但一种新型的4,9-二氨基荧光素A衍生物基于大量的G2 / M期阻滞而具有很强的抗增殖活性。由于这种生物学活性明显不同于参考化合物喜树碱，因此有力地表明至少某些褪黑素A衍生物可能是有效的抗增殖剂，但作用方式不同。
• Heterobicyclic metalloprotease inhibitors
  申请人：Gege Christian

  公开号：US20080261968A1

  公开（公告）日：2008-10-23

  The present invention relates generally to azabicyclic containing pharmaceutical agents, and in particular, to azabicyclic metalloprotease inhibiting compounds. More particularly, the present invention provides a new class of azabicyclic MMP-3, MMP-8 and/or MMP-13 inhibiting compounds, which exhibit an increased potency and selectivity in relation to currently known MMP-13, MMP-8 and MMP-3 inhibitors.

  本发明涉及含有杂环的药物，特别是含有杂环的金属蛋白酶抑制剂。更具体地说，本发明提供了一种新型的杂环MMP-3、MMP-8和/或MMP-13抑制剂，其在与当前已知的MMP-13、MMP-8和MMP-3抑制剂相比具有更高的效力和选择性。
• Small molecule BET bromodomain inhibitors and uses thereof
  申请人：ConverGene LLC

  公开号：US11028079B2

  公开（公告）日：2021-06-08

  The present invention relates to compounds that bind to and otherwise modulate the activity of bromodomain-containing proteins, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders.

  本发明涉及与含溴结构域蛋白质结合或以其他方式调节其活性的化合物、制备这些化合物的工艺、含有这些化合物的药物组合物，以及使用这些化合物治疗各种病症和疾病的方法。
• Lead optimization and efficacy evaluation of quinazoline-based BET family inhibitors for potential treatment of cancer and inflammatory diseases
  作者：Shyh-Ming Yang、Makoto Yoshioka、Jeffrey W. Strovel、Daniel J. Urban、Xin Hu、Matthew D. Hall、Ajit Jadhav、David J. Maloney

  DOI：10.1016/j.bmcl.2019.03.014

  日期：2019.5

  Extensive optimization of quinazoline-based lead 8 is described. The structure-activity relationship studies indicate the S-configuration is preferred for the phenylmorpholine substitution. Together with incorporation of a (2-hydroxyl-2-methylpropyl)pyrazole moiety at the 2-position leads to analogs with comparable potency and marked improvement in the pharmacokinetic profile over our previously reported lead compounds. Further in vivo efficacy studies in Kasumi-1 xenograft mouse model demonstrates that the selected inhibitors are well tolerated and highly efficacious in the inhibition of tumor growth. Additionally, the representative analog 19 also demonstrated significant improvement of arthritis severity in a collagen-induced arthritis (CIA) mouse model. These results indicate potential use of these quinazoline-based BET inhibitors for treatment of cancer and inflammatory diseases. A brief discussion of the co-crystallized structure of 19 with BRD4 (BD1) is also highlighted.