3-(2,2-dimethyl-3-oxoindan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester | 122732-08-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 3-(2,2-dimethyl-3-oxoindan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester
• 英文别名: 1-(2,2-dimethyl-3-oxo-indan-1-yl)-5-imidazolecarboxylic acid methyl ester；1-(2,2-Dimethyl-3-oxoindan-1-yl)-5-imidazolecarboxylic acid methyl ester；methyl 3-(2,2-dimethyl-3-oxo-1H-inden-1-yl)imidazole-4-carboxylate
• CAS: 122732-08-5
• 化学式: C₁₆H₁₆N₂O₃
• 分子量: 284.315
• InChiKey: IKJPHVQZRKVISL-UHFFFAOYSA-N

物化性质

• 沸点：
  465.7±45.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  61.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2,2-dimethyl-3-oxoindan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester 在 咪唑 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.5h， 生成 3-[5-(tert-butyl-dimethyl-silanyloxymethyl)-imidazol-1-yl]-2,2-dimethyl-indan-1-ol
  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
• 作为产物：
  描述：

  2,2-二甲基-1H-茚-1,3(2H)-二酮 在 sodium tetrahydroborate 、 偶氮二甲酸二叔丁酯 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 4.0h， 生成 3-(2,2-dimethyl-3-oxoindan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester
  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

• Method for controlling weeds
  申请人：Janssen Pharmaceutica N.V.

  公开号：US05246915A1

  公开（公告）日：1993-09-21

  A method for controlling weeds preferably in the crops of useful plants by using a 5-imidazolecarboxylic acid derivative; herbicidal compositions containing the same; novel 5-imidazolecarboxylic acid derivatives.

  一种用5-咪唑羧酸衍生物控制杂草的方法，优选在有用植物作物中使用；含有该衍生物的除草剂组合物；新颖的5-咪唑羧酸衍生物。
• Herbicidal imidazole derivatives
  申请人：Ciba-Geigy Corporation

  公开号：US04898607A1

  公开（公告）日：1990-02-06

  1,5-substituted imidazole derivatives of formula I ##STR1## the stereochemically isomeric forms thereof, and the salts thereof, have useful herbicidal properties. The substituents R.sup.1, R.sup.2, R.sup.3, R.sup.4, X.sup.1, X.sup.2, X.sup.3, A, L and m have the meanings defined herein.

  公式I中的1,5-取代咪唑衍生物 ##STR1## 其立体化学异构体及其盐具有有用的除草活性。 取代基R.sup.1、R.sup.2、R.sup.3、R.sup.4、X.sup.1、X.sup.2、X.sup.3、A、L和m的含义如本文所定义。
• Imidazole derivatives
  申请人：Ciba-Geigy Corporation

  公开号：US05000777A1

  公开（公告）日：1991-03-19

  1,5-substituted imidazole derivatives of formula I ##STR1## the stereochemically isomeric forms thereof, and the salts thereof, have useful herbicidal properties. The substituents R.sup.1, R.sup.2, R.sup.3, R.sup.4, X.sup.1, X.sup.2, X.sup.3, A, L and m have the meanings defined herein.

  公式I中的1,5-取代咪唑衍生物 ##STR1## 其立体化学异构体和其盐具有有用的除草特性。 取代基R.sup.1，R.sup.2，R.sup.3，R.sup.4，X.sup.1，X.sup.2，X.sup.3，A，L和m的含义在此定义。
• ORGANIC COMPOUNDS
  申请人：Adams Christopher

  公开号：US20100048562A1

  公开（公告）日：2010-02-25

  The present invention provides a compound of formula I: said compound is inhibitor of aldosterone synthase (CYP11B2), and/or 11 beta-hydroxylase (CYP11B1), and/or aromatase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase, aromatase, or CYP11B1. 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, fibrosis and remodeling following hypertension and endothelial dysfunction. Finally, the present invention also provides a pharmaceutical composition.

  本发明提供了一种公式I的化合物：该化合物是醛固酮合成酶（CYP11B2）和/或11β-羟化酶（CYP11B1）和/或芳香化酶的抑制剂，因此可用于治疗由醛固酮合成酶、芳香化酶或CYP11B1介导的疾病或疾病。因此，公式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：US08436035B2

  公开（公告）日：2013-05-07

  The present invention provides a compound of formula I: said compound is inhibitor of aldosterone synthase (CYP11B2), and/or 11 beta-hydroxylase (CYP11B1), and/or aromatase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase, aromatase, or CYP11B1. 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, 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I式化合物：所述化合物是醛固酮合成酶（CYP11B2）和/或11-β-羟化酶（CYP11B1）和/或芳香化酶的抑制剂，因此可用于治疗由醛固酮合成酶、芳香化酶或CYP11B1介导的疾病或疾患。因此，I式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纤维化和重塑。最后，本发明还提供了一种制药组合物。