ethyl 2-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)benzoate | 1423014-76-9

• 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 2-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)benzoate
• CAS: 1423014-76-9
• 化学式: C₁₅H₁₉NO₂
• 分子量: 245.321
• InChiKey: SWEIRHWOMXGDAH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 2-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)benzoate 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 生成 2-(2,3-dihydrobenzofuran-5-yl)ethyl 2-(1-methyl-1,2,5,6-tetrahydropyridine-4-yl)benzoate hydrochloride
  参考文献：
  名称：

  Structural Modifications to Tetrahydropyridine-3-carboxylate Esters en Route to the Discovery of M₅-Preferring Muscarinic Receptor Orthosteric Antagonists

  摘要：

  The M-5 muscarinic acetylcholine receptor is suggested to be a potential pharmacotherapeutic target for the treatment of drug abuse. We describe herein the discovery of a series of M-5-preferring orthosteric antagonists based on the scaffold of 1,2,5,6-tetrahydropyridine-3-carboxylic acid. Compound 56, the most selective compound in this series, possesses an 11-fold selectivity for the M-5 over M-1 receptor and shows little activity at M-2-M-4. This compound, although exhibiting modest affinity (K-i = 2.24 mu M) for the [H-3]N-methylscopolamine binding site on the M-5 receptor, is potent (IC50 = 0.45 nM) in inhibiting oxotremorine-evoked [H-3]DA release from rat striatal slices. Further, a homology model of human M-5 receptor based on the crystal structure of the rat M-3 receptor was constructed, and docking studies of compounds 28 and 56 were performed in an attempt to understand the possible binding mode of these novel analogues to the receptor.

  DOI：

  10.1021/jm301774u
• 作为产物：
  描述：

  2-乙氧羰基苯硼酸 在 sodium tetrahydroborate 、 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 丙酮 为溶剂， 反应 5.0h， 生成 ethyl 2-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)benzoate
  参考文献：
  名称：

  Structural Modifications to Tetrahydropyridine-3-carboxylate Esters en Route to the Discovery of M₅-Preferring Muscarinic Receptor Orthosteric Antagonists

  摘要：

  The M-5 muscarinic acetylcholine receptor is suggested to be a potential pharmacotherapeutic target for the treatment of drug abuse. We describe herein the discovery of a series of M-5-preferring orthosteric antagonists based on the scaffold of 1,2,5,6-tetrahydropyridine-3-carboxylic acid. Compound 56, the most selective compound in this series, possesses an 11-fold selectivity for the M-5 over M-1 receptor and shows little activity at M-2-M-4. This compound, although exhibiting modest affinity (K-i = 2.24 mu M) for the [H-3]N-methylscopolamine binding site on the M-5 receptor, is potent (IC50 = 0.45 nM) in inhibiting oxotremorine-evoked [H-3]DA release from rat striatal slices. Further, a homology model of human M-5 receptor based on the crystal structure of the rat M-3 receptor was constructed, and docking studies of compounds 28 and 56 were performed in an attempt to understand the possible binding mode of these novel analogues to the receptor.

  DOI：

  10.1021/jm301774u