6-(isoquinolin-4-yl)-1H-benzo[d][1,3]oxazin-2(4H)-one | 1194450-75-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 6-(isoquinolin-4-yl)-1H-benzo[d][1,3]oxazin-2(4H)-one
• 英文别名: 6-Isoquinolin-4-yl-1,4-dihydro-3,1-benzoxazin-2-one
• CAS: 1194450-75-3
• 化学式: C₁₇H₁₂N₂O₂
• 分子量: 276.294
• InChiKey: OJQULHYDJOMGHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-溴氨基苯甲酸甲酯 在 lithium aluminium tetrahydride 、 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 为溶剂， 生成 6-(isoquinolin-4-yl)-1H-benzo[d][1,3]oxazin-2(4H)-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

文献信息

• Inhibitors of the Human Aldosterone Sythase CYP11B2
  申请人：Hartmann Rolf W.

  公开号：US20110112067A1

  公开（公告）日：2011-05-12

  The invention provides compounds of the general formula (I) which are inhibitors of the human aldosterone synthase, and also pharmaceutical compositions containing these compounds, and a method of treating of hyperaldosteronism and/or disorders or diseases that are mediated by 11β-hydroxylase (CYP11B1) with these compounds.

  该发明提供了一般式(I)的化合物，这些化合物是人类醛固酮合成酶的抑制剂，还包括含有这些化合物的药物组合物，以及使用这些化合物治疗高醛固酮症和/或由11β-羟化酶（CYP11B1）介导的疾病或疾病的方法。
• 6-Pyridin-3-YL-3,4-Dihydro-1H-Quinolin-2-One Derivatives and Related Compounds as Inhibitors of the Human Aldosterone Synthase CYP11B2
  申请人：Hartmann Rolf W.

  公开号：US20110118241A1

  公开（公告）日：2011-05-19

  The invention provides compounds of the general formula (I) which are inhibitors of the human aldosterone synthase, and also pharmaceutical compositions containing these compounds, and the use of these compounds and other heteroaryl substituted quinolinone derivatives for the treatment of hyperaldosteronism and/or disorders or diseases that are mediated by 11 β-hydroxylase (CYP11 B1).

  本发明提供了一般式(I)的化合物，它们是人类醛固酮合成酶的抑制剂，还提供了含有这些化合物的制药组合物以及使用这些化合物和其他杂环取代喹啉酮衍生物治疗高醛固酮症和/或11β-羟化酶(CYP11B1)介导的疾病或疾病的方法。
• 6-PYRIDIN-3-YL-3,4-DIHYDRO-1H-QUINOLIN-2-ONE DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF THE HUMAN ALDOSTERONE SYNTHASE CYP11B2
  申请人：Universität des Saarlandes

  公开号：EP2280954B1

  公开（公告）日：2013-03-27
• US8541404B2
  申请人：——

  公开号：US8541404B2

  公开（公告）日：2013-09-24
• Heteroatom insertion into 3,4-dihydro-1H-quinolin-2-ones leads to potent and selective inhibitors of human and rat aldosterone synthase
  作者：Cornelia M. Grombein、Qingzhong Hu、Sabrina Rau、Christina Zimmer、Rolf W. Hartmann

  DOI：10.1016/j.ejmech.2014.12.022

  日期：2015.1

  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.