ethyl (1R,2R)-6'-((2-((R)-2,2-dimethylcyclopentyl)-2'-fluoro-5'-methoxy-[1,1'-biphenyl]-4-yl)methoxy)-2',3'-dihydrospiro[cyclopropane-1,1'-indene]-2-carboxylate | 1448668-63-0

• 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: ethyl (1R,2R)-6'-((2-((R)-2,2-dimethylcyclopentyl)-2'-fluoro-5'-methoxy-[1,1'-biphenyl]-4-yl)methoxy)-2',3'-dihydrospiro[cyclopropane-1,1'-indene]-2-carboxylate
• CAS: 1448668-63-0
• 化学式: C₃₅H₃₉FO₄
• 分子量: 542.691
• InChiKey: CHSCWBULZFSBSR-SVFJEUMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.14
• 重原子数：
  40.0
• 可旋转键数：
  8.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  44.76
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  ethyl (1R,2R)-6'-((2-((R)-2,2-dimethylcyclopentyl)-2'-fluoro-5'-methoxy-[1,1'-biphenyl]-4-yl)methoxy)-2',3'-dihydrospiro[cyclopropane-1,1'-indene]-2-carboxylate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 15.0h， 以11.34 g的产率得到AM-5262
  参考文献：
  名称：

  Discovery and Optimization of Potent GPR40 Full Agonists Containing Tricyclic Spirocycles

  摘要：

  GPR40 (FFAR1 or FFA1) is a target of high interest being pursued to treat type II diabetes due to its unique Mechanism leading to :little risk of hypoglycemia. We recently reported the discovery of AM-1638 (2), a potent full agonist. GPR40. In this report, we present the discovery Of GPR40 full agonists containing conformationally constrained tricyclic spirocycles and their structure- activity relationships leading to More potent agonists such as AM-5262 (26) with improved rat PK profile and general selectivity profile. AM-5262 enhanced glucose stimulated insulin secretion (mouse and human islets) and improved glucose homeostasis in vivo (OGTT in HF/STZ mice) when compared to AM-1638.,

  DOI：

  10.1021/ml300427u
• 作为产物：
  描述：

  (2-((1R)-2,2-dimethylcyclopentyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methanol 在 氯化亚砜 、 caesium carbonate 作用下， 以 正己烷 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 18.0h， 生成 ethyl (1R,2R)-6'-((2-((R)-2,2-dimethylcyclopentyl)-2'-fluoro-5'-methoxy-[1,1'-biphenyl]-4-yl)methoxy)-2',3'-dihydrospiro[cyclopropane-1,1'-indene]-2-carboxylate
  参考文献：
  名称：

  Discovery and Optimization of Potent GPR40 Full Agonists Containing Tricyclic Spirocycles

  摘要：

  GPR40 (FFAR1 or FFA1) is a target of high interest being pursued to treat type II diabetes due to its unique Mechanism leading to :little risk of hypoglycemia. We recently reported the discovery of AM-1638 (2), a potent full agonist. GPR40. In this report, we present the discovery Of GPR40 full agonists containing conformationally constrained tricyclic spirocycles and their structure- activity relationships leading to More potent agonists such as AM-5262 (26) with improved rat PK profile and general selectivity profile. AM-5262 enhanced glucose stimulated insulin secretion (mouse and human islets) and improved glucose homeostasis in vivo (OGTT in HF/STZ mice) when compared to AM-1638.,

  DOI：

  10.1021/ml300427u