6-溴-3,4-二氢喹唑啉-2-酮 | 1246765-38-7

• 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: 6-溴-3,4-二氢喹唑啉-2-酮
• 英文名称: 6-bromo-3,4-dihydroquinazolin-2(1H)-one
• 英文别名: 6-bromo-3,4-dihydro-1H-quinazolin-2-one
• CAS: 1246765-38-7
• 化学式: C₈H₇BrN₂O
• 分子量: 227.06
• InChiKey: LPMQSNAFKKEZAK-UHFFFAOYSA-N

物化性质

• 沸点：
  309.5±42.0 °C(Predicted)
• 密度：
  1.610±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  1

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P280,P305+P351+P338,P310
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  室温和干燥环境

反应信息

• 作为反应物：
  描述：

  6-溴-3,4-二氢喹唑啉-2-酮 、 3-吡啶硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 以98%的产率得到6-(pyridin-3-yl)-3,4-dihydroquinazolin-2(1H)-one
  参考文献：
  名称：

  Heteroatom insertion into 3,4-dihydro-1H-quinolin-2-ones leads to potent and selective inhibitors of human and rat aldosterone synthase

  摘要：

  Aldosterone synthase (CYP11B2) catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone. CYP11B2 is regarded as a new target for several cardiovascular diseases which are associated with chronically elevated aldosterone levels such as hypertension, congestive heart failure and myocardial fibrosis. In this paper, we optimized heterocycle substituted 3,4-dihydropyridin-2(1H)-ones as CYP11B inhibitors by systematic introduction of heteroatoms and by bioisosteric exchange of the lactame moiety by a sultame moiety. The most promising compounds regarding inhibition of human CYP11B2 and selectivity versus human enzymes CYP11B1, CYP17, and CYP19 were tested for inhibition of rat CYP11B2. Thus, we discovered compounds 4 and 9 which show potent inhibition of hCYP11B2 (IC50 < 1 nM) and the corresponding rat enzyme (4: 64%, 9: 51% inhibition, at 2 mu M). (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.022
• 作为产物：
  描述：

  3,4-二氢-1H-喹唑啉-2-酮 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以50%的产率得到6-溴-3,4-二氢喹唑啉-2-酮
  参考文献：
  名称：

  Heteroatom insertion into 3,4-dihydro-1H-quinolin-2-ones leads to potent and selective inhibitors of human and rat aldosterone synthase

  摘要：

  Aldosterone synthase (CYP11B2) catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone. CYP11B2 is regarded as a new target for several cardiovascular diseases which are associated with chronically elevated aldosterone levels such as hypertension, congestive heart failure and myocardial fibrosis. In this paper, we optimized heterocycle substituted 3,4-dihydropyridin-2(1H)-ones as CYP11B inhibitors by systematic introduction of heteroatoms and by bioisosteric exchange of the lactame moiety by a sultame moiety. The most promising compounds regarding inhibition of human CYP11B2 and selectivity versus human enzymes CYP11B1, CYP17, and CYP19 were tested for inhibition of rat CYP11B2. Thus, we discovered compounds 4 and 9 which show potent inhibition of hCYP11B2 (IC50 < 1 nM) and the corresponding rat enzyme (4: 64%, 9: 51% inhibition, at 2 mu M). (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.022

文献信息

• Rational Design of Original Fused-Cycle Selective Inhibitors of Tryptophan 2,3-Dioxygenase
  作者：Arina Kozlova、Léopold Thabault、Maxime Liberelle、Simon Klaessens、Julien R. C. Prévost、Caroline Mathieu、Luc Pilotte、Vincent Stroobant、Benoît Van den Eynde、Raphaël Frédérick

  DOI：10.1021/acs.jmedchem.1c00323

  日期：2021.8.12

  6-(1H-indol-3-yl)-benzotriazole scaffold of TDO2 inhibitors developed through rational design, starting from existing inhibitors. Rigidification of the initial scaffold led to the synthesis of stable compounds displaying a nanomolar cellular potency and a better understanding of the structural modulations that can be accommodated inside the active site of hTDO2.

  色氨酸 2,3-双加氧酶 (TDO2) 是一种含有血红素的酶，在肝脏中以高浓度组成型表达，负责l-色氨酸 ( l- Trp) 稳态。由于通过犬尿氨酸途径增强l- Trp 分解代谢，TDO2 在癌细胞中的表达导致抑制免疫介导的肿瘤排斥。在本文的研究中，我们公开了一种新的 6-(1 H-indol-3-yl)-苯并三唑支架的 TDO2 抑制剂，从现有抑制剂开始，通过合理设计开发。初始支架的硬化导致了稳定化合物的合成，显示出纳摩尔级的细胞效力，并更好地了解可以容纳在h TDO2活性位点内的结构调节。
• Synthesis of 6-Piperazinyl-3,4-dihydroquinazolin-2(1H)-ones
  作者：N. Ullah

  DOI：10.14233/ajchem.2014.15639

  日期：——

  A series of new 6-piperazinyl-3,4-dihydroquinazolin-2(1H)-ones have been synthesized. The described compounds are structurally related to adoprazine, a potential atypical antipsychotics bearing potent D2 receptor antagonist and 5-HT1A receptor agonist properties. Buchwald-Hartwig coupling of suitably modified aryl bromides with tert-butyl piperazine-1-carboxylate afforded the advanced intermediate piperazinyl-3,4-dihydroquinazolin-2(1H)-one. The reductive amination of the latter with appropriately designed biarylaldehydes accomplished the synthesis of 6-piperazinyl-3,4-dihydroquinazolin-2(1H)-ones.

  一系列新的6-哌嗪基-3,4-二氢喹唑啉-2(1H)-酮已经被合成。这些化合物在结构上与具有强效D2受体拮抗剂和5-HT1A受体激动剂特性的潜在非典型抗精神病药物adoprazine相关。通过布赫瓦尔德-哈特维希耦合，将适当改造的芳基溴化物与叔丁基哌嗪-1-羧酸酯反应，获得了中间体哌嗪基-3,4-二氢喹唑啉-2(1H)-酮。随后，使用适当设计的二芳基醛对该中间体进行还原胺化，成功合成了6-哌嗪基-3,4-二氢喹唑啉-2(1H)-酮。
• 6-PIPERAZINYL-3,4-DIHYDROQUINAZOLIN-2(1H)-ONES
  申请人：King Abdulaziz City for Science and Technology

  公开号：US20150232448A1

  公开（公告）日：2015-08-20

  A series of new 6-piperazinyl-3,4-dihydroquinazolin-2(1H)-ones have been synthesized. The compounds are structurally related to adoprazine, a potential atypical antipsychotics bearing potent D 2 receptor antagonist and 5-HT 1A receptor agonist properties. Buchwald-Hartwig coupling of suitably modified aryl bromides with tert-butyl piperazine-1-carboxylate afforded the advanced intermediate piperazinyl-3,4-dihydroquinazolin-2(1H)-one. The reductive amination of the latter with appropriately designed biarylaldehydes accomplished the synthesis of these compounds.

  已合成一系列新的6-哌嗪基-3,4-二氢喹唑啉-2(1H)-酮。这些化合物在结构上与阿多普拉辛（adoprazine）相关，后者是一种潜在的非典型抗精神病药物，具有强效的D2受体拮抗剂和5-HT1A受体激动剂性质。通过适当改性的芳基溴化物与叔丁基哌嗪-1-羧酸酯的Buchwald-Hartwig偶联反应，得到了先进的中间体哌嗪基-3,4-二氢喹唑啉-2(1H)-酮。后者与设计合理的双芳基醛进行还原胺化反应，完成了这些化合物的合成。
• 4,5-DIHYDRO-1H-PYRAZOLE COMPOUNDS AND THEIR PHARMACEUTICAL USES
  申请人：Arhancet Graciela Barbieri

  公开号：US20120022058A1

  公开（公告）日：2012-01-26

  Mineralocorticoid receptor antagonists (MRa), pharmaceutical compositions containing such inhibitors and the use of such inhibitors to treat, for example, diabetic nephropathy and hypertension in mammals, including humans.

  矿物质皮质激素受体拮抗剂（MRa），含有这种抑制剂的制药组合物以及使用这种抑制剂治疗哺乳动物（包括人类）中的糖尿病肾病和高血压。
• [EN] 4, 5-DIHYDRO-1H-PYRAZOLE COMPOUNDS AND THEIR PHARMACEUTICAL USES<br/>[FR] COMPOSÉS 4,5-DIHYDRO-LH-PYRAZOLE ET LEURS UTILISATIONS PHARMACEUTIQUES
  申请人：PFIZER

  公开号：WO2010116282A8

  公开（公告）日：2011-11-03