compound 4p | 691902-33-7

• 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: compound 4p
• 英文别名: 3-{4-[(2',6'-dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl}propanoic acid；3-[4-[(2',6'-dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl]propionic acid；3-{4-[(2'',6''-Dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl}propanoic Acid；3-[4-[[3-(2,6-dimethylphenyl)phenyl]methoxy]-2-fluorophenyl]propanoic acid
• CAS: 691902-33-7
• 化学式: C₂₄H₂₃FO₃
• 分子量: 378.443
• InChiKey: GOWIOGNRWWZDKB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2',6'-二甲基-3-联苯甲醛 在 sodium tetrahydroborate 、 lithium hydroxide monohydrate 、 三丁基膦 、 水 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 为溶剂， 反应 9.0h， 生成 compound 4p
  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

• Remedy for Diabetes
  申请人：Suzuki Nobuhiro

  公开号：US20080319077A1

  公开（公告）日：2008-12-25

  The present invention relates to a therapeutic agent for diabetes with sulfonylurea secondary failure, which contains a GPR40 agonist. According to the present invention, a therapeutic agent for diabetes with sulfonylurea secondary failure that affords a superior insulin secretion effect and a superior hypoglycemic effect even in diabetic patients for whom a sulfonylurea compound or a fast-acting insulin secretagogue fails to provide an insulin secretion effect and therefore, fails to provide a sufficient hypoglycemic effect can be provided.

  本发明涉及一种含有GPR40激动剂的治疗糖尿病二甲基磺酰脲失效的药物。根据本发明，可以提供一种治疗糖尿病二甲基磺酰脲失效的药物，即使在糖尿病患者中，磺酰脲化合物或快速作用的胰岛素分泌剂无法提供胰岛素分泌效果，因此无法提供足够的降血糖效果，本药物也能提供卓越的胰岛素分泌效果和卓越的降血糖效果。
• 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。
• 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
• US7932289B2
  申请人：——

  公开号：US7932289B2

  公开（公告）日：2011-04-26