1-Acetyl-5-trifluoromethoxy-1,3-dihydro-benzimidazol-2-one | 1060803-03-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-Acetyl-5-trifluoromethoxy-1,3-dihydro-benzimidazol-2-one
• 英文别名: 3-acetyl-6-(trifluoromethoxy)-1H-benzimidazol-2-one
• CAS: 1060803-03-3
• 化学式: C₁₀H₇F₃N₂O₃
• 分子量: 260.172
• InChiKey: QKXYHQZOJHPTPC-UHFFFAOYSA-N

物化性质

• 密度：
  1.497±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-硝基-4-(三氟甲氧基)乙酰苯胺 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 4.0h， 生成 1-Acetyl-5-trifluoromethoxy-1,3-dihydro-benzimidazol-2-one
  参考文献：
  名称：

  Benzimidazolones: A New Class of Selective Peroxisome Proliferator-Activated Receptor γ (PPARγ) Modulators

  摘要：

  A series of benzimidazolone carboxylic acids and oxazolidinediones were designed and synthesized in search of selective PPAR gamma modulators (SPPAR gamma Ms) as potential therapeutic agents for the treatment of type II diabetes mellitus (T2DM) with improved safety profiles relative to rosiglitazone and pioglitazone, the currently marketed PPAR gamma full agonist drugs. Structure activity relationships of these potent and highly selective SPPAR gamma Ms were studied with a focus on their unique profiles as partial agonists or modulators. A variety of methods, such as X-ray aystallographic analysis, PPAR gamma transactivation coactivator profiling, gene expression profiling, and mutagenesis studies, were employed to reveal the differential interactions of these new analogues with PPAR gamma receptor in comparison to full agonists. In rodent models of T2DM, benzimidazolone analogues such as (5R)-5-(3-{[3-(5-methoxybenzisoxazol-3-yl)benzimidazol-1-yl]methyl}phenyl)-5-methyloxazolidinedione (Si) demonstrated efficacy equivalent to that of rosiglitazone. Side effects, such as fluid retention and heart weight gain associated with PPAR gamma full agonists, were diminished with 51 in comparison to rosiglitazone based on studies in two independent animal models.

  DOI：

  10.1021/jm201061j

文献信息

• Benzimidazolones: A New Class of Selective Peroxisome Proliferator-Activated Receptor γ (PPARγ) Modulators
  作者：Weiguo Liu、Fiona Lau、Kun Liu、Harold B. Wood、Gaochao Zhou、Yuli Chen、Ying Li、Taro E. Akiyama、Gino Castriota、Monica Einstein、Chualin Wang、Margaret E. McCann、Thomas W. Doebber、Margaret Wu、Ching H. Chang、Lesley McNamara、Brian McKeever、Ralph T. Mosley、Joel P. Berger、Peter T. Meinke

  DOI：10.1021/jm201061j

  日期：2011.12.22

  A series of benzimidazolone carboxylic acids and oxazolidinediones were designed and synthesized in search of selective PPAR gamma modulators (SPPAR gamma Ms) as potential therapeutic agents for the treatment of type II diabetes mellitus (T2DM) with improved safety profiles relative to rosiglitazone and pioglitazone, the currently marketed PPAR gamma full agonist drugs. Structure activity relationships of these potent and highly selective SPPAR gamma Ms were studied with a focus on their unique profiles as partial agonists or modulators. A variety of methods, such as X-ray aystallographic analysis, PPAR gamma transactivation coactivator profiling, gene expression profiling, and mutagenesis studies, were employed to reveal the differential interactions of these new analogues with PPAR gamma receptor in comparison to full agonists. In rodent models of T2DM, benzimidazolone analogues such as (5R)-5-(3-[3-(5-methoxybenzisoxazol-3-yl)benzimidazol-1-yl]methyl}phenyl)-5-methyloxazolidinedione (Si) demonstrated efficacy equivalent to that of rosiglitazone. Side effects, such as fluid retention and heart weight gain associated with PPAR gamma full agonists, were diminished with 51 in comparison to rosiglitazone based on studies in two independent animal models.