6-bromo-7-ethoxy-1-methyl-3,4-dihydro-1H-quinolin-2-one | 1392223-84-5

• 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-ethoxy-1-methyl-3,4-dihydro-1H-quinolin-2-one
• 英文别名: 6-bromo-7-ethoxy-1-methyl-3,4-dihydroquinolin-2(1H)-one；6-Bromo-7-ethoxy-1-methyl-1,2,3,4-tetrahydroquinolin-2-one；6-bromo-7-ethoxy-1-methyl-3,4-dihydroquinolin-2-one
• CAS: 1392223-84-5
• 化学式: C₁₂H₁₄BrNO₂
• 分子量: 284.153
• InChiKey: UYVLABJFJCNDHL-UHFFFAOYSA-N

物化性质

• 沸点：
  475.4±45.0 °C(Predicted)
• 密度：
  1.417±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 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-ethoxy-1-methyl-3,4-dihydro-1H-quinolin-2-one 在 copper(I) oxide 、 ammonium hydroxide 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 N-甲基吡咯烷酮 、 1,2-二氯乙烷 为溶剂， 反应 6.0h， 生成 6-amino-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-ethoxy-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

• 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).
• Design of a Chemical Probe for the Bromodomain and Plant Homeodomain Finger-Containing (BRPF) Family of Proteins
  作者：Niall Igoe、Elliott D. Bayle、Cynthia Tallant、Oleg Fedorov、Julia C. Meier、Pavel Savitsky、Catherine Rogers、Yannick Morias、Sarah Scholze、Helen Boyd、Danen Cunoosamy、David M. Andrews、Anne Cheasty、Paul E. Brennan、Susanne Müller、Stefan Knapp、Paul V. Fish

  DOI：10.1021/acs.jmedchem.7b00611

  日期：2017.8.24

  bromodomain and plant homeodomain finger-containing (BRPF) family are scaffolding proteins important for the recruitment of histone acetyltransferases of the MYST family to chromatin. Here, we describe NI-57 (16) as new pan-BRPF chemical probe of the bromodomain (BRD) of the BRPFs. Inhibitor 16 preferentially bound the BRD of BRPF1 and BRPF2 over BRPF3, whereas binding to BRD9 was weaker. Compound 16 has excellent

  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