4-bromo-2-methylphthalazin-1(2H)-one

• 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: 4-bromo-2-methylphthalazin-1(2H)-one
• 英文别名: 4-bromo-2-methylphthalazin-1-one
• 化学式: C₉H₇BrN₂O
• 分子量: 239.071
• InChiKey: KMHJUYMJPHKSQS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-bromo-2-methylphthalazin-1(2H)-one 在 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 90.0h， 生成 (4-(4-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)phenoxy)butyl)triphenylphosphonium
  参考文献：
  名称：

  Development of novel proteasome inhibitors based on phthalazinone scaffold

  摘要：

  In this study we designed a series of proteasome inhibitors using pyridazinone as initial scaffold, and extended the structure with rational design by computer aided drug design (CADD). Two different synthetic routes were explored and the biological evaluation of the phthalazinone derivatives was investigated. Most importantly, electron positive triphenylphosphine group was first introduced in the structure of proteasome inhibitors and potent inhibition was achieved. As 6c was the most potent inhibitor of proteasome, we examined the structure- activity relationship (SAR) of 6c analogs. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.04.067
• 作为产物：
  描述：

  1-(2H)-酞嗪酮 在 溴 、 potassium carbonate 、 potassium bromide 作用下， 以 水 、 丙酮 为溶剂， 反应 39.5h， 生成 4-bromo-2-methylphthalazin-1(2H)-one
  参考文献：
  名称：

  合成4- alkylsulfanylphthalazin-1（2 ħ） -酮通过取代的4- bromophthalazin-1（2钯催化sulfanylation ħ） -酮

  摘要：

  描述了一系列新的烷基硫烷基酞嗪酮和酞嗪衍生物的合成。通过四个步骤有效地合成了目标化合物，包括以下步骤：（1）将2-甲酰基苯甲酸与水合肼环化以形成酞嗪酮，（2）用KBr 3直接溴化酞嗪酮核，（3）得到的烷基化产物。 4-溴内酰胺（Mitsunobu方法）制得N-以及O-烷基衍生物，最后生成（4）2-烷基-4-溴酞嗪酮和1-烷氧基-4-溴酞嗪衍生物与脂肪族硫醇的钯催化偶联反应。此外，合成了2-甲基-8-（丙-2-基）硫烷基-吡啶并[3,4- d ]吡啶并-1（2 H还描述了由2-甲基-吡啶并[3,4- d ]吡啶并嗪-1（2 H）-通过与KBr 3的溴化反应和随后在催化偶合反应条件下由异丙基硫醇进行的磺酰化反应制得的1 ）-酮。

  DOI：

  10.1016/j.tet.2016.10.022

文献信息

• New Pyridinones and Isoquinolinones as Inhibitors of the Bromodomain BRD9
  申请人：Boehringer Ingelheim International GmbH

  公开号：US20180044335A1

  公开（公告）日：2018-02-15

  The present invention encompasses compounds of general formula (I) wherein the groups R 1 to R 9 , X 1 and X 2 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation, e.g. cancer, pharmaceutical preparations containing such compounds and their uses as a medicament.

  本发明涵盖了一般式（I）的化合物，其中基团R1至R9，X1和X2的含义如权利要求和说明书中所述。本发明的化合物适用于治疗由细胞过度或异常增殖所特征化的疾病，例如癌症，含有这种化合物的制药制剂以及它们作为药物的用途。
• Synthesis of 4-alkylsulfanylphthalazin-1(2H)-ones via palladium catalyzed sulfanylation of substituted 4-bromophthalazin-1(2H)-ones
  作者：Zbigniew Malinowski、Emilia Fornal、Beata Sierocińska、Renata Czeczko、Monika Nowak

  DOI：10.1016/j.tet.2016.10.022

  日期：2016.12

  The synthesis of a series of new alkylsulfanyl phthalazinone and phthalazine derivatives is described. The target compounds were efficiently synthesized in a four step sequence, consisting of (1) cyclization of 2-formylbenzoic acid with hydrazine hydrate to form phthalazinone, (2) the direct bromination of phthalazinone core with KBr3, (3) alkylation of the obtained 4-bromolactam (Mitsunobu procedure)

  描述了一系列新的烷基硫烷基酞嗪酮和酞嗪衍生物的合成。通过四个步骤有效地合成了目标化合物，包括以下步骤：（1）将2-甲酰基苯甲酸与水合肼环化以形成酞嗪酮，（2）用KBr 3直接溴化酞嗪酮核，（3）得到的烷基化产物。 4-溴内酰胺（Mitsunobu方法）制得N-以及O-烷基衍生物，最后生成（4）2-烷基-4-溴酞嗪酮和1-烷氧基-4-溴酞嗪衍生物与脂肪族硫醇的钯催化偶联反应。此外，合成了2-甲基-8-（丙-2-基）硫烷基-吡啶并[3,4- d ]吡啶并-1（2 H还描述了由2-甲基-吡啶并[3,4- d ]吡啶并嗪-1（2 H）-通过与KBr 3的溴化反应和随后在催化偶合反应条件下由异丙基硫醇进行的磺酰化反应制得的1 ）-酮。
• Pyridinones and isoquinolinones as inhibitors of the bromodomain BRD9
  申请人：Boehringer Ingelheim International GmbH

  公开号：US11319318B2

  公开（公告）日：2022-05-03

  The present invention encompasses compounds of general formula (I) wherein the groups R1 to R9, X1 and X2 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation, e.g. cancer, pharmaceutical preparations containing such compounds and their uses as a medicament.

  本发明包括通式（I）的化合物，其中基团 R1 至 R9、X1 和 X2 具有权利要求书和说明书中给出的含义。本发明的化合物适用于治疗以细胞过度增殖或异常增殖为特征的疾病（如癌症）、含有此类化合物的药物制剂及其作为药物的用途。
• Phthalazinone Pyrazoles as Potent, Selective, and Orally Bioavailable Inhibitors of Aurora-A Kinase
  作者：Michael E. Prime、Stephen M. Courtney、Frederick A. Brookfield、Richard W. Marston、Victoria Walker、Justin Warne、Andrew E. Boyd、Norman A. Kairies、Wolfgang von der Saal、Anja Limberg、Guy Georges、Richard A. Engh、Bernhard Goller、Petra Rueger、Matthias Rueth

  DOI：10.1021/jm101346r

  日期：2011.1.13

  The inhibition of Aurora kinases in order to arrest mitosis and subsequently inhibit tumor growth via apoptosis of proliferating cells has generated significant discussion within the literature. We report a novel class of Aurora kinase inhibitors based upon a phthalazinone pyrazole scaffold. The development of the phthalazinone template resulted in a potent Aurora-A selective series of compounds (typically >1000-fold selectivity over Aurora-B) that display good pharmacological profiles with significantly improved oral bioavailability compared to the well studied Aurora inhibitor VX-680.
• NEW PYRIDINONES AND ISOQUINOLINONES AS INHIBITORS OF THE BROMODOMAIN BRD9
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP3265453B1

  公开（公告）日：2022-06-29