(E)-1-(1-adamantyl)-3-(6-methoxypyridin-3-yl)prop-2-en-1-one | 1012864-80-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (E)-1-(1-adamantyl)-3-(6-methoxypyridin-3-yl)prop-2-en-1-one
• CAS: 1012864-80-0
• 化学式: C₁₉H₂₃NO₂
• 分子量: 297.397
• InChiKey: UXPXYDNAJGOGLZ-DUXPYHPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-1-(1-adamantyl)-3-(6-methoxypyridin-3-yl)prop-2-en-1-one 、 三甲基碘化亚砜 在 sodium hydride 作用下， 以 二甲基亚砜 、 mineral oil 为溶剂， 反应 12.25h， 以90%的产率得到adamantan-1-yl-[2-(6-methoxy-pyridin-3-yl)-cyclopropyl]-methanone
  参考文献：
  名称：

  Synergism of virtual screening and medicinal chemistry: Identification and optimization of allosteric antagonists of metabotropic glutamate receptor 1

  摘要：

  We report the identification of novel potent and selective metabotropic glutamate receptor 1 (mGluR1) antagonists by virtual screening and subsequent hit optimization. For ligand-based virtual screening, molecules were represented by a topological pharmacophore descriptor (CATS-2D) and clustered by a self-organizing map (SOM). The most promising compounds were tested in mGluR1 functional and binding assays. We identified a potent chemotype exhibiting selective antagonistic activity at mGluR1 ( functional IC50 = 0.74 +/- 0.29 mu M). Hit optimization yielded lead structure 16 with an affinity of K-i = 0.024 +/- 0.001 mu M and greater than 1000-fold selectivity for mGluR1 versus mGluR5. Homology-based receptor modelling suggests a binding site compatible with previously reported mutation studies. Our study demonstrates the usefulness of ligand-based virtual screening for scaffold-hopping and rapid lead structure identification in early drug discovery projects. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.05.072