2-{1-[5-(tert-butyldimethylsilanyloxymethyl)imidazol-1-yl]-2-hydroxy-2-methylpropyl}benzonitrile | 952494-00-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-{1-[5-(tert-butyldimethylsilanyloxymethyl)imidazol-1-yl]-2-hydroxy-2-methylpropyl}benzonitrile
• 英文别名: 2-{1-[5-(tert-butyl-dimethyl-silanyloxymethyl)-imidazol-1-yl]-2-hydroxy-2-methyl-propyl}-benzonitrile；2-(1-(5-(((tert-butyldimethylsilyl)oxy)methyl)-1H-imidazol-1-yl)-2-hydroxy-2-methylpropyl)benzonitrile；2-[1-[5-[[tert-butyl(dimethyl)silyl]oxymethyl]imidazol-1-yl]-2-hydroxy-2-methylpropyl]benzonitrile
• CAS: 952494-00-7
• 化学式: C₂₁H₃₁N₃O₂Si
• 分子量: 385.582
• InChiKey: OSWGBVPTBNHMFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.64
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  71.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-{1-[5-(tert-butyldimethylsilanyloxymethyl)imidazol-1-yl]-2-hydroxy-2-methylpropyl}benzonitrile 在 palladium on activated charcoal manganese(IV) oxide 、 硫酸 、 氢气 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 38.17h， 生成 4-(5-butyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one
  参考文献：
  名称：

  WO2007/117982

  摘要：

  公开号：
• 作为产物：
  描述：

  4-(tert-butyldimethylsilyloxymethyl)-1-(triphenylmethyl)imidazole 在 二乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 、 乙腈 为溶剂， 反应 18.0h， 生成 2-{1-[5-(tert-butyldimethylsilanyloxymethyl)imidazol-1-yl]-2-hydroxy-2-methylpropyl}benzonitrile
  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