isopropyl 9-anti-({5-methyl-6-[(2-methylpyridin-3-yl)oxy]-pyrimidin-4-yl}oxy)-3-oxa-7-azabicyclo[3.3.1]nonane-7-carboxylate | 1147553-15-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: isopropyl 9-anti-({5-methyl-6-[(2-methylpyridin-3-yl)oxy]-pyrimidin-4-yl}oxy)-3-oxa-7-azabicyclo[3.3.1]nonane-7-carboxylate
• CAS: 1147553-15-8
• 化学式: C₂₂H₂₈N₄O₅
• 分子量: 428.488
• InChiKey: RDCVTCCVZBQMNZ-IZZQQSIFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.15
• 重原子数：
  31.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  95.9
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  3-oxa-7-azabicyclo[3.3.1]nonan-9-ol 在 sodium hexamethyldisilazane 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 甲苯 为溶剂， 反应 15.3h， 生成 isopropyl 9-anti-({5-methyl-6-[(2-methylpyridin-3-yl)oxy]-pyrimidin-4-yl}oxy)-3-oxa-7-azabicyclo[3.3.1]nonane-7-carboxylate
  参考文献：
  名称：

  Activation of the G-Protein-Coupled Receptor 119: A Conformation-Based Hypothesis for Understanding Agonist Response

  摘要：

  The synthesis and properties of the bridged piperidine (oxaazabicyclo) compounds 8, 9, and 11 are described. A conformational analysis of these structures is compared with the representative GPR119 ligand 1. These results and the differences in agonist pharmacology are used to formulate a conformation-based hypothesis to understand activation of the GPR119 receptor. We also show for these structures that the agonist pharmacology in rat masks the important differences in human pharmacology.

  DOI：

  10.1021/jm200003p

文献信息

• [EN] BICYCLIC HETEROCYCLE DERIVATIVES AND THEIR USE AS MODULATORS OF THE ACTIVITY OF GPR119<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES BICYCLIQUES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：SCHERING CORP

  公开号：WO2009055331A3

  公开（公告）日：2009-07-30
• Activation of the G-Protein-Coupled Receptor 119: A Conformation-Based Hypothesis for Understanding Agonist Response
  作者：Kim F. McClure、Etzer Darout、Cristiano R. W. Guimarães、Michael P. DeNinno、Vincent Mascitti、Michael J. Munchhof、Ralph P. Robinson、Jeffrey Kohrt、Anthony R. Harris、Dianna E. Moore、Bryan Li、Lacey Samp、Bruce A. Lefker、Kentaro Futatsugi、Daniel Kung、Paul D. Bonin、Peter Cornelius、Ruduan Wang、Eben Salter、Sam Hornby、Amit S. Kalgutkar、Yue Chen

  DOI：10.1021/jm200003p

  日期：2011.3.24

  The synthesis and properties of the bridged piperidine (oxaazabicyclo) compounds 8, 9, and 11 are described. A conformational analysis of these structures is compared with the representative GPR119 ligand 1. These results and the differences in agonist pharmacology are used to formulate a conformation-based hypothesis to understand activation of the GPR119 receptor. We also show for these structures that the agonist pharmacology in rat masks the important differences in human pharmacology.