6-bromo-7-methoxy-1-methyl-3,4-dihydro-1H-quinolin-2-one | 1392223-83-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 6-bromo-7-methoxy-1-methyl-3,4-dihydro-1H-quinolin-2-one
• 英文别名: 6-bromo-7-methoxy-1-methyl-3,4-dihydroquinolin-2(1H)-one；6-Bromo-7-methoxy-1-methyl-1,2,3,4-tetrahydroquinolin-2-one；6-bromo-7-methoxy-1-methyl-3,4-dihydroquinolin-2-one
• CAS: 1392223-83-4
• 化学式: C₁₁H₁₂BrNO₂
• 分子量: 270.126
• InChiKey: JPXWREWDTVNWQS-UHFFFAOYSA-N

物化性质

• 沸点：
  471.0±45.0 °C(Predicted)
• 密度：
  1.468±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-bromo-7-methoxy-1-methyl-3,4-dihydro-1H-quinolin-2-one 在 三溴化硼 、 sodium hydride 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 正庚烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 6.0h， 生成 6-bromo-7-ethoxy-1-methylquinolin-2(1H)-one
  参考文献：
  名称：

  溴结构域和植物同源域指状蛋白（BRPF）家族的化学探针的设计

  摘要：

  含溴结构域和植物同源结构域的手指（BRPF）家族是支架蛋白，对于将MYST家族的组蛋白乙酰基转移酶募集到染色质中非常重要。在这里，我们将NI-57（16）描述为BRPF的溴结构域（BRD）的新pan-BRPF化学探针。与BRPF3相比，抑制剂16优先结合BRPF1和BRPF2的BRD，而与BRD9的结合较弱。化合物16对非IV类BRD蛋白具有出色的选择性。在nanoBRET和FRAP分析中证明了BRPF1B和BRPF2与16的靶标结合。绑定16通过X射线共晶结构确定，对BRPF1B的合成进行了合理化，与以前的结构相比，该结构显示出翻转的结合方向。我们报告的研究表明16在癌症和炎症模型中通过在低微摩尔浓度下调节表型在细胞测定中具有功能活性。在小鼠中单剂给药产生了16种药代动力学数据，显示出良好的口服生物利用度

  DOI：

  10.1021/acs.jmedchem.7b00611
• 作为产物：
  描述：

  3,4-二氢-7-羟基-2(1H)-喹啉酮 在 N-溴代丁二酰亚胺(NBS) 、 potassium tert-butylate 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 6-bromo-7-methoxy-1-methyl-3,4-dihydro-1H-quinolin-2-one
  参考文献：
  名称：

  Selective Dual Inhibitors of CYP19 and CYP11B2: Targeting Cardiovascular Diseases Hiding in the Shadow of Breast Cancer

  摘要：

  Postmenopausal women are at high risk for cardiovascular diseases because of the estrogen deficiency. As for postmenopausal breast cancer patients, this risk is even higher due to inhibition of estrogens biosyntheses in peripheral tissue by the aromatase (CYP19) inhibitors applied. Because estrogen deficiency results in significantly elevated aldosterone levels, which are a major cause of cardiovascular diseases, dual inhibition of CYP19 and CYP11B2 (aldosterone synthase) is a promising treatment for breast cancer and the coinstantaneous cardiovascular diseases. By combination of important structural features of known CYP19 and CYP11B2 inhibitors, we succeeded in obtaining compounds 3 and 5 as selective dual inhibitors with IC50 values around 50 and 20 nM toward CYP19 and CYP11B2, respectively. These compounds showed also good selectivity toward CYP11B1 (selectivity factors (IC50 (CYP11B1)/IC50 (CYP11B2)) around 50) and CYP17 (no inhibition).

  DOI：

  10.1021/jm3004637

文献信息

• [EN] 1,4-DISUBSTITUTED PYRIDAZINE DERIVATIVES AND THEIR USE FOR TREATING SMN-DEFICIENCY-RELATED CONDITIONS<br/>[FR] DÉRIVÉS DE PYRIDAZINE 1,4-DISUBSTITUÉS ET LEUR UTILISATION POUR LE TRAITEMENT DE PATHOLOGIES LIÉES À UNE DÉFICIENCE EN SMN
  申请人：NOVARTIS AG

  公开号：WO2015017589A1

  公开（公告）日：2015-02-05

  The present invention provides a compound of formula IA or a pharmaceutically acceptable salt thereof; 5 (IA) a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了一种公式IA的化合物或其药用盐；5（IA）一种制造本发明化合物的方法及其治疗用途。本发明进一步提供了一种药物活性剂的组合物和药物组合物。
• 1,4-DISUBSTITUTED PYRIDAZINE QUINOLNE ANALOGS THERE OF AND METHODS FOR TREATING SMN-DEFICIENCY-RELATED CONDITIONS
  申请人：CHEUNG Atwood

  公开号：US20160184305A1

  公开（公告）日：2016-06-30

  The present invention provides a compound of formula IA or a pharmaceutically acceptable salt thereof; 5 (IA) a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了式IA的化合物或其药学上可接受的盐；一种制造本发明化合物的方法以及其治疗用途。本发明还提供了一种药理活性剂的组合和一种制药组合物。
• 1,4-DISUBSTITUTED PYRIDAZINE DERIVATIVES AND THEIR USE FOR TREATING SMN-DEFICIENCY-RELATED CONDITIONS
  申请人：Novartis AG

  公开号：EP3027600A1

  公开（公告）日：2016-06-08
• PYRIMIDINE DERIVATIVES AS PGE2 RECEPTOR MODULATORS
  申请人：IDORSIA PHARMACEUTICALS LTD

  公开号：US20210113559A1

  公开（公告）日：2021-04-22

  The present invention relates to pyrimidine derivatives of formula (I) wherein (R 1 ) n , R 3 , R 4a , R 4b , R 5a , R 5b and Ar 1 are as described in the description and their use in the treatment of cancer by modulating an immune response comprising a reactivation of the immune system in the tumor. The invention further relates to novel benzofurane and benzothiophene derivatives of formula (II) and their use as pharmaceuticals, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as modulators of the prostaglandin 2 receptors EP2 and/or EP4.
• Selective Dual Inhibitors of CYP19 and CYP11B2: Targeting Cardiovascular Diseases Hiding in the Shadow of Breast Cancer
  作者：Qingzhong Hu、Lina Yin、Rolf W. Hartmann

  DOI：10.1021/jm3004637

  日期：2012.8.23

  Postmenopausal women are at high risk for cardiovascular diseases because of the estrogen deficiency. As for postmenopausal breast cancer patients, this risk is even higher due to inhibition of estrogens biosyntheses in peripheral tissue by the aromatase (CYP19) inhibitors applied. Because estrogen deficiency results in significantly elevated aldosterone levels, which are a major cause of cardiovascular diseases, dual inhibition of CYP19 and CYP11B2 (aldosterone synthase) is a promising treatment for breast cancer and the coinstantaneous cardiovascular diseases. By combination of important structural features of known CYP19 and CYP11B2 inhibitors, we succeeded in obtaining compounds 3 and 5 as selective dual inhibitors with IC50 values around 50 and 20 nM toward CYP19 and CYP11B2, respectively. These compounds showed also good selectivity toward CYP11B1 (selectivity factors (IC50 (CYP11B1)/IC50 (CYP11B2)) around 50) and CYP17 (no inhibition).