3-[(2,4,5,6-tetrahydro-4-oxo-1H-pyrrolo[3,2,1-ij]quinolin-8-yl)(1H-imidazol-1-yl)methyl]benzonitrile | 1194451-04-1

• 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: 3-[(2,4,5,6-tetrahydro-4-oxo-1H-pyrrolo[3,2,1-ij]quinolin-8-yl)(1H-imidazol-1-yl)methyl]benzonitrile
• 英文别名: 3-[Imidazol-1-yl-(11-oxo-1-azatricyclo[6.3.1.04,12]dodeca-4,6,8(12)-trien-6-yl)methyl]benzonitrile
• CAS: 1194451-04-1
• 化学式: C₂₂H₁₈N₄O
• 分子量: 354.411
• InChiKey: BODHDTKMCNGJSG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  61.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  咯喹酮 在 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 氯化亚砜 、 六正丁基二锡 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 6.0h， 生成 3-[(2,4,5,6-tetrahydro-4-oxo-1H-pyrrolo[3,2,1-ij]quinolin-8-yl)(1H-imidazol-1-yl)methyl]benzonitrile
  参考文献：
  名称：

  Novel Imidazol-1-ylmethyl Substituted 1,2,5,6-Tetrahydropyrrolo[3,2,1-ij]quinolin-4-ones as Potent and Selective CYP11B1 Inhibitors for the Treatment of Cushing’s Syndrome

  摘要：

  CYP11B1 inhibition is a promising therapy for Cushing's syndrome. Starting from etomidate, references I and II, the title compounds were designed and synthesized. Cyclopropyl analogue 4 was identified as a CYP11B1 inhibitor more potent (IC50 = 2.2 nM) than leads and more selective (SF = 11) than I and metyrapone. Since it also showed potent inhibition of rat CYP11B1 and good selectivity over human CYP17 and CYP19, it is a promising candidate for further development.

  DOI：

  10.1021/jm3003872

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
• Novel Imidazol-1-ylmethyl Substituted 1,2,5,6-Tetrahydropyrrolo[3,2,1-<i>ij</i>]quinolin-4-ones as Potent and Selective CYP11B1 Inhibitors for the Treatment of Cushing’s Syndrome
  作者：Lina Yin、Simon Lucas、Frauke Maurer、Uli Kazmaier、Qingzhong Hu、Rolf W. Hartmann

  DOI：10.1021/jm3003872

  日期：2012.7.26

  CYP11B1 inhibition is a promising therapy for Cushing's syndrome. Starting from etomidate, references I and II, the title compounds were designed and synthesized. Cyclopropyl analogue 4 was identified as a CYP11B1 inhibitor more potent (IC50 = 2.2 nM) than leads and more selective (SF = 11) than I and metyrapone. Since it also showed potent inhibition of rat CYP11B1 and good selectivity over human CYP17 and CYP19, it is a promising candidate for further development.