3-[trans-2-(2,4-difluorophenyl)vinyl]-5-(2-methoxy-(1S)-methyl-ethoxy)-N-(nicotinic acid-6-yl)-benzamide | 1282520-10-8

• 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-[trans-2-(2,4-difluorophenyl)vinyl]-5-(2-methoxy-(1S)-methyl-ethoxy)-N-(nicotinic acid-6-yl)-benzamide
• 英文别名: 6-[[3-[(E)-2-(2,4-difluorophenyl)ethenyl]-5-[(2S)-1-methoxypropan-2-yl]oxybenzoyl]amino]pyridine-3-carboxylic acid
• CAS: 1282520-10-8
• 化学式: C₂₅H₂₂F₂N₂O₅
• 分子量: 468.457
• InChiKey: HKCJXSWTKIPQLN-BWPKMQGJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  97.8
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-羟基间苯二甲酸二甲酯 在 吡啶 、 氯化亚砜 、 硼烷四氢呋喃络合物 、 偶氮二甲酸二异丙酯 、 potassium tert-butylate 、 水 、 sodium methylate 、 三溴化磷 、 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-[trans-2-(2,4-difluorophenyl)vinyl]-5-(2-methoxy-(1S)-methyl-ethoxy)-N-(nicotinic acid-6-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

• Discovery of a novel phenylethyl benzamide glucokinase activator for the treatment of type 2 diabetes mellitus
  作者：Kaapjoo Park、Byoung Moon Lee、Young Hwan Kim、Taedong Han、Wonhui Yi、Dong Hoon Lee、Hyun Ho Choi、Wonee Chong、Chun Ho Lee

  DOI：10.1016/j.bmcl.2012.11.018

  日期：2013.1

  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.