6-bromobenzo[h]quinazolin-4(3H)-one | 1227924-40-4

• 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: 6-bromobenzo[h]quinazolin-4(3H)-one
• 英文别名: 6-bromo-3H-benzo[h]quinazolin-4-one
• CAS: 1227924-40-4
• 化学式: C₁₂H₇BrN₂O
• 分子量: 275.104
• InChiKey: JOIGXBRFEHJLTD-UHFFFAOYSA-N

物化性质

• 沸点：
  473.6±47.0 °C(Predicted)
• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-bromobenzo[h]quinazolin-4(3H)-one 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 rac-3-[(1R,2R)-2-hydroxycyclohexyl]-6-vinylbenzo[h]quinazolin-4(3H)-one
  参考文献：
  名称：

  [EN] AMINOBENZOQUINAZOLINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
  [FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1 À BASE D'AMINOBENZOQUINAZOLINONE

  摘要：

  本发明涉及式(I)的氨基苯并喹唑醌酮化合物，其为M1受体阳性变构调节剂，并且在治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍等方面有用。该发明还涉及包含这些化合物的药物组合物，以及在治疗M1受体介导的疾病中使用这些化合物和组合物。

  公开号：

  WO2011084371A1
• 作为产物：
  描述：

  ethyl 1-[(tert-butoxycarbonyl)amino]naphthalene-2-carboxylate 在 N-溴代丁二酰亚胺(NBS) 、 碳酸氢铵 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 20.33h， 生成 6-bromobenzo[h]quinazolin-4(3H)-one
  参考文献：
  名称：

  Substituted benzoquinazolinones. Part 1: Synthesis of 6-aminobenzo[h]quinazolinones via Buchwald–Hartwig amination from 6-bromobenzo[h]quinazolinones

  摘要：

  6-(Morpholin-4-yl)benzothlquinazolin-4(3H)-one derivatives 18a,b were prepared under Buchwald-Hartwig conditions by reacting 6-bromobenzo[h]quinazolin-4(3H)-ones 13a,b with morpholine in the presence of a Pd(OAc)(2)/XantPhos system in 1,4-dioxane as solvent. The starting 6-bromobenzo[h] quinazolin-4(3H)-ones 13 were synthesized via condensation of the ethyl 1-amino-4-bromonaphthalene-2-carboxylate (11) with formamide (Niementowski reaction), and then reaction of the obtained benzoquinazolinone 9 with appropriates benzyl bromides. Compound 11 was prepared using a three-step procedure involving (a) metalation of the N-Boc- or N-Piv-protected 1-aminonaphthalenes with t-BuLi, followed by reaction with ethyl chloroformate, (b) bromination of the naphthalene ring of ester 3 using NBS, and next (c) deprotecion of the amine group with TFA or HCI. Biological screening of the potential cytotoxicity of compounds 8, 9, 18b on A549 and HT29 cell lines, as well as on the lymphocytes showed that compound 18b has interesting anticancer activities. The detailed synthesis, spectroscopic data, and biological assays were reported. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2014.05.117

文献信息

• [EN] ARYL METHYL BENZOQUINAZOLINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1 D'ARYLMÉTHYLBENZOQUINAZOLINONE
  申请人：MERCK SHARP & DOHME

  公开号：WO2010059773A1

  公开（公告）日：2010-05-27

  The present invention is directed to benzoquinazilinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的苯并喹噁唑啉酮化合物，这些化合物是M1受体阳性变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。该发明还涉及包含这些化合物的药物组合物，以及在治疗由M1受体介导的疾病中使用这些化合物和组合物。
• Substituted benzoquinazolinones. Part 2: Synthesis of amino-, and sulfanyl-derivatives of benzo[f]- and benzo[h]quinazolinones
  作者：Monika Nowak、Zbigniew Malinowski、Emilia Fornal、Andrzej Jóźwiak、Ewa Parfieniuk、Gabriela Gajek、Renata Kontek

  DOI：10.1016/j.tet.2015.10.049

  日期：2015.12

  the presence of KOt-Bu, in 1,4-dioxane as a solvent, at 90–100 °C. The 8-bromobenzo[f]quinazolin-1(2H)-one 15 was synthesized via condensation of the ethyl or tert-butyl 2-amino-8-bromonaphthalene-1-carboxylate 6, 10 with formamide, followed by reaction with 3,4-dimethoxybenzyl bromide. However, the 6-bromobenzo[h]quinazolin-4(3H)-ones 19a, 19b were prepared from ethyl 4-bromo-1-[(tert-butoxycarbo

  氨基和benzoquinazolinones的硫烷基-衍生物16A - Ç，20A - Ç和21A - ç使用bromobenzoquinazolinones钯催化的Buchwald-Hartwig偶联反应制备下15，图19A，19B和1-取代的哌嗪或硫醇。Pd（OAc）2与XantPhos的组合被证明是最有效的方法，可在90-100°C的KO t -Bu存在下，在1,4-二恶烷中作为溶剂使用。 8溴苯并[ ˚F ]喹唑啉-1（2 ħ） -酮15经由乙基的缩合或合成叔丁基2-氨基-8-溴萘-1-甲酸叔丁酯6，10与甲酰胺中，然后用3反应，4-二甲氧基苄基溴。然而，由4-溴-1-[[（叔丁氧基羰基）氨基]萘-2-羧酸乙酯（17）制备6-溴苯并[ h ]喹唑啉-4（3H）-酮19a，19b。 化合物16a，20a，20c对HT29和HCT116细胞系的潜在细胞毒性的生物学筛选显示，化合物20a具有显着的抗癌活性。
• [EN] PYRANYL ARYL METHYL BENZOQUINAZOLINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DE RÉCEPTEUR M1 DE TYPE PYRANYL-ARYL-MÉTHYL-BENZOQUINAZOLINONE
  申请人：MERCK SHARP & DOHME

  公开号：WO2011025851A1

  公开（公告）日：2011-03-03

  The present invention is directed to pyranyl aryl methyl benzoquinazolinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式（I）的吡喃基芳基甲基苯并喹唑啉酮化合物，这些化合物是M1受体阳性变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。该发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在治疗由M1受体介导的疾病中的用途。
• PYRANYL ARYL METHYL BENZOQUINAZOLINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
  申请人：Kuduk Scott D.

  公开号：US20120157438A1

  公开（公告）日：2012-06-21

  The present invention is directed to pyranyl aryl methyl benzoquinazolinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的吡喃基苯基甲基苯并喹唑酮化合物，它们是M1受体正向变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。该发明还涉及包括该化合物的制药组合物，以及使用该化合物和组合物治疗M1受体介导的疾病。
• Aminobenzoquinazolinone M1 Receptor Positive Allosteric Modulators
  申请人：Kuduk Scott D.

  公开号：US20120264761A1

  公开（公告）日：2012-10-18

  The present invention is directed to aminobenzoquinazolinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的氨基苯并喹唑酮化合物，它们是M1受体正向变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。本发明还涉及包含该化合物的制药组合物，以及在治疗M1受体介导的疾病中使用该化合物和组合物的方法。