(1R,1aR,6aS)-3-((2-(5,5-dimethylcyclopent-1-en-1-yl)-2'-fluoro-5'-methoxy-[1,1'-biphenyl]-4-yl)methoxy)-1,1a,6,6a-tetrahydrocyclopropa[a]indene-1-carboxylic acid | 1435274-29-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (1R,1aR,6aS)-3-((2-(5,5-dimethylcyclopent-1-en-1-yl)-2'-fluoro-5'-methoxy-[1,1'-biphenyl]-4-yl)methoxy)-1,1a,6,6a-tetrahydrocyclopropa[a]indene-1-carboxylic acid
• 英文别名: (1R,1aR,6aS)-3-[[3-(5,5-dimethylcyclopenten-1-yl)-4-(2-fluoro-5-methoxyphenyl)phenyl]methoxy]-1,1a,6,6a-tetrahydrocyclopropa[a]indene-1-carboxylic acid
• CAS: 1435274-29-5
• 化学式: C₃₂H₃₁FO₄
• 分子量: 498.594
• InChiKey: YTEOUTFTINDAON-NPBSGPTKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-羟基-1-茚酮 在 咪唑 、 sodium tetrahydroborate 、 dirhodium(II) tetracarboxylate 、 四丁基氟化铵 、 水 、 caesium carbonate 、 甲基磺酰氯 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 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 69.0h， 生成 (1R,1aR,6aS)-3-((2-(5,5-dimethylcyclopent-1-en-1-yl)-2'-fluoro-5'-methoxy-[1,1'-biphenyl]-4-yl)methoxy)-1,1a,6,6a-tetrahydrocyclopropa[a]indene-1-carboxylic acid
  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

文献信息

• Discovery and Optimization of Potent GPR40 Full Agonists Containing Tricyclic Spirocycles
  作者：Yingcai Wang、Jiwen (Jim) Liu、Paul J. Dransfield、Liusheng Zhu、Zhongyu Wang、Xiaohui Du、Xianyun Jiao、Yongli Su、An-rong Li、Sean P. Brown、Annie Kasparian、Marc Vimolratana、Ming Yu、Vatee Pattaropong、Jonathan B. Houze、Gayathri Swaminath、Thanhvien Tran、Khanh Nguyen、Qi Guo、Jane Zhang、Run Zhuang、Frank Li、Lynn Miao、Michael D. Bartberger、Tiffany L. Correll、David Chow、Simon Wong、Jian Luo、Daniel C.-H. Lin、Julio C. Medina

  DOI：10.1021/ml300427u

  日期：2013.6.13

  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.,