3-[2-(2,4-difluorophenyl)ethyl]-5-(2-methoxy-(1S)-methyl-ethoxy)-N-(1-methyl-1H-pyrazol-3-yl)-benzamide | 1282520-26-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 3-[2-(2,4-difluorophenyl)ethyl]-5-(2-methoxy-(1S)-methyl-ethoxy)-N-(1-methyl-1H-pyrazol-3-yl)-benzamide
• 英文别名: 3-[2-(2,4-difluorophenyl)ethyl]-5-[(2S)-1-methoxypropan-2-yl]oxy-N-(1-methylpyrazol-3-yl)benzamide
• CAS: 1282520-26-6
• 化学式: C₂₃H₂₅F₂N₃O₃
• 分子量: 429.467
• InChiKey: UJMGLCKQJJRDLB-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  65.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-羟基间苯二甲酸二甲酯 在 吡啶 、 硼烷四氢呋喃络合物 、 偶氮二甲酸二异丙酯 、 palladium on activated charcoal 、 potassium tert-butylate 、 水 、 氢气 、 sodium methylate 、 三溴化磷 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三苯基膦 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 生成 3-[2-(2,4-difluorophenyl)ethyl]-5-(2-methoxy-(1S)-methyl-ethoxy)-N-(1-methyl-1H-pyrazol-3-yl)-benzamide
  参考文献：
  名称：

  Discovery of a novel phenylethyl benzamide glucokinase activator for the treatment of type 2 diabetes mellitus

  摘要：

  Novel benzamide derivatives were synthesized and tested at in vitro assay by measuring fold increase of glucokinase activity at 5.0 mM glucose concentration. Among the prepared compounds, YH-GKA was found to be an active glucokinase activator with EC50 of 70 nM. YH-GKA showed similar glucose AUC reduction of 29.6% (50 mg/kg) in an OGTT study with C57BL/J6 mice compared to 29.9% for metformin (300 mg/kg). Acute treatment of the compound in C57BL/J6 and ob/ob mice elicited basal glucose lowering activity. In subchronic study with ob/ob mice, YH-GKA showed significant decrease in blood glucose levels and no adverse effects on serum lipids or body weight. In addition, YH-GKA exhibited high bioavailability and moderate elimination in preclinical species. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.018

文献信息

• NOVEL GLUCOKINASE ACTIVATORS AND PROCESSES FOR THE PREPARATION THEREOF
  申请人：Yi Won-Hui

  公开号：US20120178765A1

  公开（公告）日：2012-07-12

  The present invention provides an amide derivative having a stilbene or 1,2-diphenylethane moiety within the molecule thereof, a process for the preparation thereof, and a pharmaceutical composition comprising the same. The amide derivative of the present invention activates glucokinase remarkably, and therefore they can be usefully applied for treating glucokinase-mediated diseases, such as hyperglycemia and diabetes.

  本发明提供了一种具有分子中的一苯乙烯或1,2-二苯乙烷基团的酰胺衍生物，以及其制备方法和包含该衍生物的药物组合物。本发明的酰胺衍生物显著激活葡萄糖激酶，因此它们可以被有用地应用于治疗葡萄糖激酶介导的疾病，如高血糖和糖尿病。
• [EN] NOVEL GLUCOKINASE ACTIVATORS AND PROCESSES FOR THE PREPARATION THEREOF<br/>[FR] NOUVEAUX ACTIVATEURS DE GLUCOKINASE ET PROCÉDÉS POUR LES PRÉPARER
  申请人：YUHAN CORP

  公开号：WO2011081280A2

  公开（公告）日：2011-07-07

  The present invention provides an amide derivative having a stilbene or 1,2-diphenylethane moiety within the molecule thereof, a process for the preparation thereof, and a pharmaceutical composition comprising the same. The amide derivative of the present invention activates glucokinase remarkably, and therefore they can be usefully applied for treating glucokinase-mediated diseases, such as hyperglycemia and diabetes.