4-[5-(1-hydroxyethyl)imidazol-1-yl]-3,3-dimethylisochroman-1-one | 952492-41-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 4-[5-(1-hydroxyethyl)imidazol-1-yl]-3,3-dimethylisochroman-1-one
• 英文别名: 4-[5-(1-hydroxy-ethyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one；4-[5-(1-hydroxyethyl)imidazol-1-yl]-3,3-dimethyl-4H-isochromen-1-one
• CAS: 952492-41-0
• 化学式: C₁₆H₁₈N₂O₃
• 分子量: 286.331
• InChiKey: KRCBGJCFLJBYRP-UHFFFAOYSA-N

物化性质

• 沸点：
  533.8±50.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[5-(1-hydroxyethyl)imidazol-1-yl]-3,3-dimethylisochroman-1-one 在 manganese dioxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 以to give 4-(5-acetyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one as a white solid的产率得到4-(5-acetylimidazol-1-yl)-3,3-dimethylisochroman-1-one
  参考文献：
  名称：

  ORGANIC COMPOUNDS

  摘要：

  本发明提供了一种式为(I)的化合物：该化合物是醛固酮合成酶的抑制剂，因此可用于治疗由醛固酮合成酶介导的紊乱或疾病。因此，式(I)的化合物可用于治疗低钾血症、高血压、充血性心力衰竭、肾衰竭，特别是慢性肾衰竭、再狭窄、动脉粥样硬化、X综合征、肥胖症、肾病、心肌梗死后、冠心病、胶原形成增加、高血压和内皮功能障碍后的心脏纤维化和重塑。最后，本发明还提供了一种制药组合物。

  公开号：

  US20090182007A1
• 作为产物：
  描述：

  4-(5-hydroxymethylimidazol-1-yl)-3,3-dimethylisochroman-1-one 在 manganese(IV) oxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二丁醚 、 丙酮 为溶剂， 反应 16.0h， 生成 4-[5-(1-hydroxyethyl)imidazol-1-yl]-3,3-dimethylisochroman-1-one
  参考文献：
  名称：

  Structure–Activity Relationships, Pharmacokinetics, and in Vivo Activity of CYP11B2 and CYP11B1 Inhibitors

  摘要：

  CYP11B2, the aldosterone synthase, and CYP11B1, the cortisol synthase, are two highly homologous enzymes implicated in a range of cardiovascular and metabolic diseases. We have previously reported the discovery of LCI699, a dual CYP11B2 and CYP11B1 inhibitor that has provided clinical validation for the lowering of plasma aldosterone as a viable approach to modulate blood pressure in humans, as well normalization of urinary cortisol in Cushing's disease patients. We now report novel series of aldosterone synthase inhibitors with single-digit nanomolar cellular potency and excellent physicochemical properties. Structure-activity relationships and optimization of their oral bioavailability are presented. An illustration of the impact of the age of preclinical models on pharmacokinetic properties is also highlighted. Similar biochemical potency was generally observed against CYP11B2 and CYP11B1, although emerging structure-selectivity relationships were noted leading to more CYP11B1-selective analogs.

  DOI：

  10.1021/acs.jmedchem.5b00407

文献信息

• Organic compounds
  申请人：Novartis AG

  公开号：US08153674B2

  公开（公告）日：2012-04-10

  The present invention provides a compound of formula (I): said compound is inhibitor of aldosterone synthase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase. Accordingly, the compound of formula I can be used in treatment of hypokalemia, hypertension, congestive heart failure, renal failure, in particular, chronic renal failure, restenosis, atherosderosis, syndrome X, obesity, nephropathy, post-myocardial infarction, coronary heart diseases, increased formation of collagen, cardiac fibrosis and remodeling following hypertension and endothelial dysfunction. Finally, the present invention also provides a pharmaceutical composition.

  本发明提供了一种式(I)的化合物：该化合物是醛固酮合酶的抑制剂，因此可用于治疗由醛固酮合酶介导的疾病或疾病。因此，式I的化合物可用于治疗低钾血症，高血压，充血性心力衰竭，肾衰竭，特别是慢性肾衰竭，再狭窄，动脉粥样硬化，X综合症，肥胖症，肾病，心肌梗死后，冠心病，胶原形成增多，高血压和内皮功能障碍后的心脏纤维化和重塑。最后，本发明还提供了一种制药组合物。
• ORGANIC COMPOUNDS
  申请人：Adams Christopher

  公开号：US20090182007A1

  公开（公告）日：2009-07-16

  The present invention provides a compound of formula (I): said compound is inhibitor of aldosterone synthase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase. Accordingly, the compound of formula I can be used in treatment of hypokalemia, hypertension, congestive heart failure, renal failure, in particular, chronic renal failure, restenosis, atherosderosis, syndrome X, obesity, nephropathy, post-myocardial infarction, coronary heart diseases, increased formation of collagen, cardiac fibrosis and remodeling following hypertension and endothelial dysfunction. Finally, the present invention also provides a pharmaceutical composition.

  本发明提供了一种式为(I)的化合物：该化合物是醛固酮合成酶的抑制剂，因此可用于治疗由醛固酮合成酶介导的紊乱或疾病。因此，式(I)的化合物可用于治疗低钾血症、高血压、充血性心力衰竭、肾衰竭，特别是慢性肾衰竭、再狭窄、动脉粥样硬化、X综合征、肥胖症、肾病、心肌梗死后、冠心病、胶原形成增加、高血压和内皮功能障碍后的心脏纤维化和重塑。最后，本发明还提供了一种制药组合物。
• WO2007/117982
  申请人：——

  公开号：——

  公开（公告）日：——
• US8153674B2
  申请人：——

  公开号：US8153674B2

  公开（公告）日：2012-04-10
• [EN] ORGANIC COMPOUNDS<br/>[FR] COMPOSÉS ORGANIQUES
  申请人：NOVARTIS AG

  公开号：WO2007117982A2

  公开（公告）日：2007-10-18

  [EN] The present invention provides a compound of formula (I):said compound is inhibitor of aldosterone synthase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase. Accordingly, the compound of formula I can be used in treatment of hypokalemia, hypertension, congestive heart failure, renal failure, in particular, chronic renal failure, restenosis, atherosclerosis, syndrome X, obesity, nephropathy, post-myocardial infarction, coronary heart diseases, increased formation of collagen, cardiac fibrosis and remodeling following hypertension and endothelial dysfunction. Finally, the present invention also provides a pharmaceutical composition.
  [FR] La présente invention concerne un composé de formule (I) : ledit composé étant un inhibiteur de l'aldostérone synthase et pouvant donc être employé pour le traitement d'un trouble ou d'une maladie médié par l'aldostérone synthase. Par conséquent, le composé de formule (I) peut être utilisé dans le traitement de l'hypokaliémie, de l'hypertension, d'une insuffisance cardiaque congestive, d'une insuffisance rénale, en particulier d'une insuffisance rénale chronique, de la resténose, de l'athérosclérose, de l'angine microvasculaire, de l'obésité, de la néphropathie, du syndrome de Dressler, de maladies coronariennes, d'une formation accrue de collagène, d'une fibrose cardiaque et d'un remodelage à la suite d'une hypertension et d'un dysfonctionnement endothélial. Enfin, la présente invention concerne également une composition pharmaceutique.