ethyl 4-phenyl-1,2,5,6-tetrahydropyridine-3-carboxylate | 1423014-09-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: ethyl 4-phenyl-1,2,5,6-tetrahydropyridine-3-carboxylate
• 英文别名: Ethyl 4-phenyl-1,2,3,6-tetrahydropyridine-5-carboxylate；ethyl 4-phenyl-1,2,3,6-tetrahydropyridine-5-carboxylate
• CAS: 1423014-09-8
• 化学式: C₁₄H₁₇NO₂
• 分子量: 231.294
• InChiKey: CSAMFWKQNHHXHO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 4-phenyl-1,2,5,6-tetrahydropyridine-3-carboxylate 在 4-二甲氨基吡啶 、 sodium cyanoborohydride 、 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-(4-methoxyphenoxy)ethyl 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine-3-carboxylate 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：

  1-叔-丁基3-乙基4-(((三氟甲基)磺酰)氧代)-5,6-二氢吡啶-1,3(2H)-二甲酸基酯 在 四(三苯基膦)钯 、 sodium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 ethyl 4-phenyl-1,2,5,6-tetrahydropyridine-3-carboxylate
  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

文献信息

• Structural Modifications to Tetrahydropyridine-3-carboxylate Esters en Route to the Discovery of M₅-Preferring Muscarinic Receptor Orthosteric Antagonists
  作者：Guangrong Zheng、Andrew M. Smith、Xiaoqin Huang、Karunai L. Subramanian、Kiran B. Siripurapu、Agripina Deaciuc、Chang-Guo Zhan、Linda P. Dwoskin

  DOI：10.1021/jm301774u

  日期：2013.2.28

  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.