1,2,5,6-tetrahydro-8-(hydroxy(pyridin-4-yl)methyl)pyrrolo[3,2,1-ij]quinolin-4-one | 1194451-08-5

• 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: 1,2,5,6-tetrahydro-8-(hydroxy(pyridin-4-yl)methyl)pyrrolo[3,2,1-ij]quinolin-4-one
• 英文别名: 6-[Hydroxy(pyridin-4-yl)methyl]-1-azatricyclo[6.3.1.04,12]dodeca-4,6,8(12)-trien-11-one
• CAS: 1194451-08-5
• 化学式: C₁₇H₁₆N₂O₂
• 分子量: 280.326
• InChiKey: LMKFQLJABRFIRD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  53.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,2,5,6-tetrahydro-8-(hydroxy(pyridin-4-yl)methyl)pyrrolo[3,2,1-ij]quinolin-4-one 在 三乙基硅烷 、 三氟甲磺酸 、 三氟乙酸 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 48.0h， 以55%的产率得到1,2,5,6-tetrahydro-8-((pyridin-4-yl)methyl)pyrrolo[3,2,1-ij]quinolin-4-one
  参考文献：
  名称：

  Inhibitors of the Human Aldosterone Sythase CYP11B2

  摘要：

  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。

  公开号：

  US20110112067A1
• 作为产物：
  描述：

  氯化异氰盐酸盐 在 甲醇 、 aluminum (III) chloride 、 sodium tetrahydroborate 作用下， 反应 5.0h， 生成 1,2,5,6-tetrahydro-8-(hydroxy(pyridin-4-yl)methyl)pyrrolo[3,2,1-ij]quinolin-4-one
  参考文献：
  名称：

  Tetrahydropyrroloquinolinone Type Dual Inhibitors of Aromatase/Aldosterone Synthase as a Novel Strategy for Breast Cancer Patients with Elevated Cardiovascular Risks

  摘要：

  The application of aromatase inhibitors to postmenopausal breast cancer patients increases the risk of cardiovascular diseases (CVD), which is believed to be caused by the abnormally high concentrations of aldosterone as a consequence of the estrogen deficiency. Dual inhibitors of aromatase (CYP19) and aldosterone synthase (CYP11B2) are therefore proposed as a novel strategy for the adjuvant therapy to reduce the CVD risk for these patients. By combining decisive structural features of CYP11B2 and CYP19 inhibitors into a common template, a series of pyridinylmethyl substituted 1,2,5,6-tetrahydro-pyrrolo [3,2,1-ij]quinolin-4-ones were designed and synthesized. Interestingly, the substituents on the methylene bridge showed strong influences on the inhibitory activities leading to opposite effects, that is, a given substituent showed an increase in inhibition of one enzyme, while it led to a decrease for the other enzyme. The compromise of this conflict led to compounds 3j, 3k, 3n, and 3p as potent and selective dual inhibitors of CYP19 and CYP11B2, especially compound 3p, which exhibited IC50 values of 32 and 41 nM for CYP19 and CYP11B2, respectively, and a high selectivity toward CYP17 and CYP11B1. This compound is considered as a candidate for further evaluation in vivo.

  DOI：

  10.1021/jm301408t

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。
• [EN] 6-PYRIDIN-3-YL-3,4-DIHYDRO-1H-QUINOLIN-2-ONE DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF THE HUMAN ALDOSTERONE SYNTHASE CYP11B2<br/>[FR] DÉRIVÉS DE 6-PYRIDIN-3-YL-3,4-DIHYDRO-1H-QUINOLIN-2-ONE ET COMPOSÉS APPARENTÉS EN TANT QU'INHIBITEURS DE L'ALDOSTÉRONE SYNTHASE CYP11B2 HUMAINE
  申请人：UNIV SAARLAND

  公开号：WO2009135651A8

  公开（公告）日：2010-01-21
• 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