(±)-exo-ethyl 3-hydroxy-1,1a,6,6a-tetrahydrocyclopropa[a]indene-1-carboxylate | 1435276-24-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (±)-exo-ethyl 3-hydroxy-1,1a,6,6a-tetrahydrocyclopropa[a]indene-1-carboxylate
• CAS: 1435276-24-6
• 化学式: C₁₃H₁₄O₃
• 分子量: 218.252
• InChiKey: WTOWHPRXEBENSX-WOPDTQHZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.84
• 重原子数：
  16.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (±)-exo-ethyl 3-hydroxy-1,1a,6,6a-tetrahydrocyclopropa[a]indene-1-carboxylate 在 水 、 caesium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 为溶剂， 反应 31.0h， 生成 (1S,1aS,6aR)-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
• 作为产物：
  描述：

  6-羟基-1-茚酮 在 甲醇 、 sodium tetrahydroborate 、 (CuOTf)*toluene 、 palladium on activated charcoal 、 氢气 、 potassium carbonate 、 对甲苯磺酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 45.5h， 生成 (±)-exo-ethyl 3-hydroxy-1,1a,6,6a-tetrahydrocyclopropa[a]indene-1-carboxylate
  参考文献：
  名称：

  [EN] FUSED TRICYCLIC COMPOUNDS AS RAF KINASE INHIBITORS
  [FR] COMPOSÉS TRICYCLIQUES FUSIONNÉS À UTILISER EN TANT QU'INHIBITEURS DE LA KINASE RAF

  摘要：

  提供了某些融合的三环化合物及其盐，以及它们的组合物和使用方法。

  公开号：

  WO2013097224A1

文献信息

• [EN] FUSED TRICYCLIC COMPOUNDS AS RAF KINASE INHIBITORS<br/>[FR] COMPOSÉS TRICYCLIQUES FUSIONNÉS À UTILISER EN TANT QU'INHIBITEURS DE LA KINASE RAF
  申请人：BEIGENE LTD

  公开号：WO2013097224A1

  公开（公告）日：2013-07-04

  Provided are certain fused tricyclic compounds and salts thereof, compositions thereof, and methods of use therefor.

  提供了某些融合的三环化合物及其盐，以及它们的组合物和使用方法。
• FUSED TRICYCLIC COMPOUNDS AS RAF KINASE INHIBITORS
  申请人：BEIGENE, LTD.

  公开号：US20150045355A1

  公开（公告）日：2015-02-12

  Provided are certain fused tricyclic compounds and salts thereof, compositions thereof, and methods of use therefor.

  提供了某些融合的三环化合物及其盐，以及它们的组合物和使用方法。
• 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.,