methyl 4-[[3-(2-thienyl)phenyl]methoxy]benzenepropanoate | 691904-13-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: methyl 4-[[3-(2-thienyl)phenyl]methoxy]benzenepropanoate
• 英文别名: Methyl 3-[4-[(3-thiophen-2-ylphenyl)methoxy]phenyl]propanoate
• CAS: 691904-13-9
• 化学式: C₂₁H₂₀O₃S
• 分子量: 352.454
• InChiKey: DDTPDTZXTISWAH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  63.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4-[[3-(2-thienyl)phenyl]methoxy]benzenepropanoate 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 以17%的产率得到3-(4-{[3-(thiophen-2-yl)benzyl]oxy}phenyl)propanoic acid
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of Potent and Orally Available G Protein-Coupled Receptor 40 Agonists

  摘要：

  G protein-coupled receptor 40 (GPR40) is being recently considered to be a new potential drug target for the treatment of type 2 diabetes because of its role in the enhancement of free fatty acid-regulated glucose-stimulated insulin secretion in pancreatic beta-cells. We initially identified benzyloxyphenylproparoic acid (1b) (EC50 = 510 nM), which was designed based on the structure of free fatty acids, as a promising lead compound with GPR40 agonist activity. Chemical modification of compound 1b led to the discovery of 3-{4-[(2',6'-dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl}propanoic acid (4p) as a potent GPR40 agonist (EC50 = 5,7 nM). Compound 4p exhibited acceptable pharmacokinetic profiles and significant glucose-lowering effects during an oral glucose tolerance test in diabetic rat;. Moreover, no hypoglycemic event was observed even after administration of a high dose of compound 4p to normal fasted rats. These pharmacological results suggest that GPR40 agonists might be novel glucose-dependent insulin secretagogues with little or no risk of hypoglycemia.

  DOI：

  10.1021/jm101405t
• 作为产物：
  描述：

  3-溴苯甲醇 在 四(三苯基膦)钯 、 三丁基膦 、 sodium carbonate 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 为溶剂， 生成 methyl 4-[[3-(2-thienyl)phenyl]methoxy]benzenepropanoate
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of Potent and Orally Available G Protein-Coupled Receptor 40 Agonists

  摘要：

  G protein-coupled receptor 40 (GPR40) is being recently considered to be a new potential drug target for the treatment of type 2 diabetes because of its role in the enhancement of free fatty acid-regulated glucose-stimulated insulin secretion in pancreatic beta-cells. We initially identified benzyloxyphenylproparoic acid (1b) (EC50 = 510 nM), which was designed based on the structure of free fatty acids, as a promising lead compound with GPR40 agonist activity. Chemical modification of compound 1b led to the discovery of 3-{4-[(2',6'-dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl}propanoic acid (4p) as a potent GPR40 agonist (EC50 = 5,7 nM). Compound 4p exhibited acceptable pharmacokinetic profiles and significant glucose-lowering effects during an oral glucose tolerance test in diabetic rat;. Moreover, no hypoglycemic event was observed even after administration of a high dose of compound 4p to normal fasted rats. These pharmacological results suggest that GPR40 agonists might be novel glucose-dependent insulin secretagogues with little or no risk of hypoglycemia.

  DOI：

  10.1021/jm101405t

文献信息

• Alkoxyphenylpropanoic Acid Derivatives
  申请人：Yasuma Tsuneo

  公开号：US20070213364A1

  公开（公告）日：2007-09-13

  The present invention aims at provision of a novel compound having a GPR40 receptor function modulating action, which is useful as an insulin secretagogue, an agent for the prophylaxis or treatment of diabetes and the like. The compound represented by the formula: wherein each symbol is as defined in the description, a salt thereof, and a prodrug thereof of the present invention unexpectedly have a superior GPR40 receptor agonistic activity and superior properties as pharmaceutical products such as stability and the like, and can be safe and useful pharmaceutical agents as agents for the prophylaxis or treatment of GPR40 receptor-related pathology or diseases in mammals.

  本发明旨在提供一种新型化合物，具有GPR40受体功能调节作用，可用作胰岛素分泌剂，用于预防或治疗糖尿病等药物。本发明的化合物由以下式表示：其中每个符号如描述中所定义，其盐和其前药，意外地具有优越的GPR40受体激动活性和优越的药物特性，如稳定性等，并且可以作为安全和有用的药物代理剂，用于哺乳动物的GPR40受体相关病理或疾病的预防或治疗。
• Receptor Function Regulator
  申请人：Fukatsu Kohji

  公开号：US20090012093A1

  公开（公告）日：2009-01-08

  The GPR40 receptor function regulator of the present invention, which comprises a compound having an aromatic ring and a group capable of releasing cation is useful as an insulin secretagogue or an agent for the prophylaxis or treatment of diabetes and the like.

  本发明的GPR40受体功能调节剂包括具有芳香环和能够释放阳离子的基团的化合物，可用作胰岛素分泌剂或预防或治疗糖尿病等疾病的药剂。
• Alkoxyphenylpropanoic acid derivatives
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2253315A1

  公开（公告）日：2010-11-24

  The present invention aims at provision of a novel compound having a GPR40 receptor function modulating action, which is useful as an insulin secretagogue, an agent for the prophylaxis or treatment of diabetes and the like. The compound represented by the formula: wherein each symbol is as defined in the description, a salt thereof, and a prodrug thereof of the present invention unexpectedly have a superior GPR40 receptor agonistic activity and superior properties as pharmaceutical products such as stability and the like, and can be safe and useful pharmaceutical agents as agents for the prophylaxis or treatment of GPR40 receptor-related pathology or diseases in mammals.

  本发明旨在提供一种新型化合物，该化合物具有调节 GPR40 受体功能的作用，可用作胰岛素分泌剂、预防或治疗糖尿病的药物等。该化合物由式表示： 其中各符号如描述中所定义的本发明的化合物、其盐及其原药出乎意料地具有优异的 GPR40 受体激动活性和作为药剂产品的优异特性，如稳定性等，可作为预防或治疗哺乳动物 GPR40 受体相关病理或疾病的药剂，是安全有用的药剂。
• GPR40 Receptor function regulator
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2385032A1

  公开（公告）日：2011-11-09

  The GPR40 receptor function regulator of the present invention, which comprises a compound having an aromatic ring and a group capable of releasing cation is useful as an insulin secretagogue or an agent for the prophylaxis or treatment of diabetes and the like.

  本发明的 GPR40 受体功能调节剂由具有芳香环和能够释放阳离子的基团的化合物组成，可用作胰岛素分泌剂或预防或治疗糖尿病等的药物。
• RECEPTOR FUNCTION CONTROLLING AGENT
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1559422B1

  公开（公告）日：2014-04-30