γ-oxo-9H-xanthene-2-butanoic acid methyl ester | 101723-87-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: γ-oxo-9H-xanthene-2-butanoic acid methyl ester
• 英文别名: γ-Oxo-xanthenyl-(2)-buttersaeure-methylester；4-oxo-4-xanthen-2-yl-butyric acid methyl ester；methyl 4-oxo-4-(9H-xanthen-2-yl)butanoate
• CAS: 101723-87-9
• 化学式: C₁₈H₁₆O₄
• 分子量: 296.323
• InChiKey: HQMLMTWXGUZPMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  γ-oxo-9H-xanthene-2-butanoic acid methyl ester 在 丙酸 、 三氯氧磷 作用下， 反应 26.0h， 生成 [1-(3-Trifluoromethyl-phenyl)-3-(9H-xanthen-2-yl)-1H-pyrazol-4-yl]-acetic acid methyl ester
  参考文献：
  名称：

  The Effect of 1,3-Diaryl-[1H]-pyrazole-4-acetamides on Glucose Utilization in ob/ob Mice

  摘要：

  This article provides evidence of a new class of compounds, 1,3-diaryl-[1H]-pyrazole-4-acetamides, initially identified from their ability to increase glucose transport in an adipocyte and muscle cell line and ultimately demonstrating dramatic glucose lowering in ob/ob Mice, a diabetic animal model. The lead compound, 1, possessed some behavioral-like effects which were removed by structural variation during the course of this investigation. Specifically, 11 g (RI = meta-CF3, Ar2 = 4 ' biphenyl, R3 = diethylamide) illustrated the potency of this series with ED50 values for glucose lowering in ob/ob mice of 3.0 mg/kg/day. Concomitant with its effect on glucose lowering, 11g also caused a 50% reduction in insulin levels consistent with an agent that increases whole body insulin sensitivity. 11g showed favorable pharmacokinetic data with acceptable absorption, negligible metabolism, and good duration of action. 11g demonstrated no appreciable adipogenic effect through PPAR gamma agonism, a characteristic of the thiazolidinediones (TZD), and so represents a potentially new class of agents for the treatment of diabetes.

  DOI：

  10.1021/jm010032c
• 作为产物：
  描述：

  氧杂蒽 、 丁二酸单甲酯酰氯 在 三氯化铝 作用下， 以 1,1,2,2-四氯乙烷 为溶剂， 反应 3.0h， 以90%的产率得到γ-oxo-9H-xanthene-2-butanoic acid methyl ester
  参考文献：
  名称：

  The Effect of 1,3-Diaryl-[1H]-pyrazole-4-acetamides on Glucose Utilization in ob/ob Mice

  摘要：

  This article provides evidence of a new class of compounds, 1,3-diaryl-[1H]-pyrazole-4-acetamides, initially identified from their ability to increase glucose transport in an adipocyte and muscle cell line and ultimately demonstrating dramatic glucose lowering in ob/ob Mice, a diabetic animal model. The lead compound, 1, possessed some behavioral-like effects which were removed by structural variation during the course of this investigation. Specifically, 11 g (RI = meta-CF3, Ar2 = 4 ' biphenyl, R3 = diethylamide) illustrated the potency of this series with ED50 values for glucose lowering in ob/ob mice of 3.0 mg/kg/day. Concomitant with its effect on glucose lowering, 11g also caused a 50% reduction in insulin levels consistent with an agent that increases whole body insulin sensitivity. 11g showed favorable pharmacokinetic data with acceptable absorption, negligible metabolism, and good duration of action. 11g demonstrated no appreciable adipogenic effect through PPAR gamma agonism, a characteristic of the thiazolidinediones (TZD), and so represents a potentially new class of agents for the treatment of diabetes.

  DOI：

  10.1021/jm010032c

文献信息

• The Effect of 1,3-Diaryl-[1H]-pyrazole-4-acetamides on Glucose Utilization in ob/ob Mice
  作者：Gregory R. Bebernitz、Greg Argentieri、Beverly Battle、Christine Brennan、Bork Balkan、Bryan F. Burkey、Michele Eckhardt、Jiaping Gao、Prasad Kapa、Robert J. Strohschein、Herbert F. Schuster、Mary Wilson、David D. Xu

  DOI：10.1021/jm010032c

  日期：2001.8.1

  This article provides evidence of a new class of compounds, 1,3-diaryl-[1H]-pyrazole-4-acetamides, initially identified from their ability to increase glucose transport in an adipocyte and muscle cell line and ultimately demonstrating dramatic glucose lowering in ob/ob Mice, a diabetic animal model. The lead compound, 1, possessed some behavioral-like effects which were removed by structural variation during the course of this investigation. Specifically, 11 g (RI = meta-CF3, Ar2 = 4 ' biphenyl, R3 = diethylamide) illustrated the potency of this series with ED50 values for glucose lowering in ob/ob mice of 3.0 mg/kg/day. Concomitant with its effect on glucose lowering, 11g also caused a 50% reduction in insulin levels consistent with an agent that increases whole body insulin sensitivity. 11g showed favorable pharmacokinetic data with acceptable absorption, negligible metabolism, and good duration of action. 11g demonstrated no appreciable adipogenic effect through PPAR gamma agonism, a characteristic of the thiazolidinediones (TZD), and so represents a potentially new class of agents for the treatment of diabetes.