3-{4-[(E)-2-(2',6'-dimethylbiphenyl-3-yl)ethenyl]phenyl}propanoic acid | 1269763-65-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 3-{4-[(E)-2-(2',6'-dimethylbiphenyl-3-yl)ethenyl]phenyl}propanoic acid
• 英文别名: 3-[4-[(E)-2-[3-(2,6-dimethylphenyl)phenyl]ethenyl]phenyl]propanoic acid
• CAS: 1269763-65-6
• 化学式: C₂₅H₂₄O₂
• 分子量: 356.464
• InChiKey: UMXVIMKTFKYOEX-BUHFOSPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-{4-[(E)-2-(2',6'-dimethylbiphenyl-3-yl)ethenyl]phenyl}propanoic acid 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 水 为溶剂， 以77%的产率得到3-{4-[2-(2',6'-dimethylbiphenyl-3-yl)ethyl]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：

  2-(3-溴苯基)乙酰氯 在 aluminum (III) chloride 、 sodium tetrahydroborate 、 四(三苯基膦)钯 、 lithium hydroxide monohydrate 、 水 、 sodium carbonate 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 硝基甲烷 、 乙醇 、 水 、 甲苯 为溶剂， 反应 7.5h， 生成 3-{4-[(E)-2-(2',6'-dimethylbiphenyl-3-yl)ethenyl]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

文献信息

• Design, Synthesis, and Biological Activity of Potent and Orally Available G Protein-Coupled Receptor 40 Agonists
  作者：Shinobu Sasaki、Shuji Kitamura、Nobuyuki Negoro、Masami Suzuki、Yoshiyuki Tsujihata、Nobuhiro Suzuki、Takashi Santou、Naoyuki Kanzaki、Masataka Harada、Yasuhiro Tanaka、Makoto Kobayashi、Norio Tada、Miyuki Funami、Toshimasa Tanaka、Yoshio Yamamoto、Kohji Fukatsu、Tsuneo Yasuma、Yu Momose

  DOI：10.1021/jm101405t

  日期：2011.3.10

  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.