(3-chlorosulfonyl-phenyl)acetic acid ethyl ester | 1190373-83-1

• 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: (3-chlorosulfonyl-phenyl)acetic acid ethyl ester
• 英文别名: ethyl 2-(3-chlorosulfonylphenyl)acetate
• CAS: 1190373-83-1
• 化学式: C₁₀H₁₁ClO₄S
• mdl: MFCD20389813
• 分子量: 262.714
• InChiKey: QPZRMBNQECBUGT-UHFFFAOYSA-N

物化性质

• 沸点：
  361.3±25.0 °C(Predicted)
• 密度：
  1.344±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  68.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  苯乙酸乙酯 在 氯磺酸 作用下， 以 二氯甲烷 为溶剂， 生成 (3-chlorosulfonyl-phenyl)acetic acid ethyl ester 、 ethyl 2-(4-(chlorosulfonyl)phenyl)acetate
  参考文献：
  名称：

  Investigation of Functionally Liver Selective Glucokinase Activators for the Treatment of Type 2 Diabetes

  摘要：

  Type 2 diabetes is a polygenic disease which afflicts nearly 200 million people worldwide and is expected to increase to near epidemic levels over the next 10-15 years. Glucokinase (GK) activators are currently under investigation by a number of pharmaceutical companies with only a few reaching early clinical evaluation. A GK activator has the promise of potentially affecting both the beta-cells of the pancreas, by improving glucose sensitive insulin secretion, as well as the liver, by reducing uncontrolled glucose output and restoring post-prandial glucose uptake and storage as glycogen. Herein, we report our efforts on a sulfonamide chemotype with the aim to generate liver selective GK activators which culminated in the discovery of 3-cyclopentyl-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)-2-[4-(4-methylpiperazine-1-sulfonyl)-phenyl]-propionamide (17c). This compound activated the GK enzyme (alpha K(a) = 39 nM) in vitro at low nanomolar concentrations and significantly reduced glucose levels during an oral glucose tolerance test in normal mice.

  DOI：

  10.1021/jm900839k

文献信息

• Investigation of Functionally Liver Selective Glucokinase Activators for the Treatment of Type 2 Diabetes
  作者：Gregory R. Bebernitz、Valerie Beaulieu、Bethany A. Dale、Richard Deacon、Alokesh Duttaroy、Jiaping Gao、Melissa S. Grondine、Ramesh C. Gupta、Mesut Kakmak、Michael Kavana、Louise C. Kirman、Jinsheng Liang、Wieslawa M. Maniara、Siralee Munshi、Sunil S. Nadkarni、Herbert F. Schuster、Travis Stams、Irene St. Denny、Paul M. Taslimi、Brian Vash、Shari L. Caplan

  DOI：10.1021/jm900839k

  日期：2009.10.8

  Type 2 diabetes is a polygenic disease which afflicts nearly 200 million people worldwide and is expected to increase to near epidemic levels over the next 10-15 years. Glucokinase (GK) activators are currently under investigation by a number of pharmaceutical companies with only a few reaching early clinical evaluation. A GK activator has the promise of potentially affecting both the beta-cells of the pancreas, by improving glucose sensitive insulin secretion, as well as the liver, by reducing uncontrolled glucose output and restoring post-prandial glucose uptake and storage as glycogen. Herein, we report our efforts on a sulfonamide chemotype with the aim to generate liver selective GK activators which culminated in the discovery of 3-cyclopentyl-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)-2-[4-(4-methylpiperazine-1-sulfonyl)-phenyl]-propionamide (17c). This compound activated the GK enzyme (alpha K(a) = 39 nM) in vitro at low nanomolar concentrations and significantly reduced glucose levels during an oral glucose tolerance test in normal mice.