methyl 3-{bis[(4-methylnaphthalen-1-yl)carbonyl]amino}pyrazine-2-carboxylate | 1416989-76-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl 3-{bis[(4-methylnaphthalen-1-yl)carbonyl]amino}pyrazine-2-carboxylate
• 英文别名: Methyl 3-[bis(4-methylnaphthalene-1-carbonyl)amino]pyrazine-2-carboxylate；methyl 3-[bis(4-methylnaphthalene-1-carbonyl)amino]pyrazine-2-carboxylate
• CAS: 1416989-76-8
• 化学式: C₃₀H₂₃N₃O₄
• 分子量: 489.53
• InChiKey: ZERXMFHJEPVDRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  89.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 3-{bis[(4-methylnaphthalen-1-yl)carbonyl]amino}pyrazine-2-carboxylate 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 一水合肼 作用下， 以 1,4-二氧六环 、 四氯化碳 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 6.5h， 生成 methyl 3-({4-[(methylthio)methyl]-1-naphthoyl}-amino)pyrazine-2-carboxylate
  参考文献：
  名称：

  Discovery of Agonists of Cannabinoid Receptor 1 with Restricted Central Nervous System Penetration Aimed for Treatment of Gastroesophageal Reflux Disease

  摘要：

  Agonists of the cannabinoid receptor 1 (CB1) have been suggested as possible treatments for a range of medical disorders including gastroesophageal reflux disease (GERD). While centrally acting cannabinoid agonists are known to produce psychotropic effects, it has been suggested that the CB1 receptors in the periphery could play a significant role in reducing reflux. A moderately potent and highly lipophilic series of 2-aminobenzamides was identified through focused screening of GPCR libraries. Development of this series focused on improving potency and efficacy at the CB1 receptor, reducing lipophilicity and limiting the central nervous system (CNS) exposure while maintaining good oral absorption. Improvement of the series led to compounds having excellent potency at the CB1 receptor and high levels of agonism, good physical and pharmacokinetic properties, and low penetration into the CNS. A range of compounds demonstrated a dose-dependent inhibition of transient lower esophageal sphincter relaxations in a dog model.

  DOI：

  10.1021/jm301511h
• 作为产物：
  描述：

  3-氨基吡嗪-2-羧酸甲酯 、 4-甲基-1-萘甲酰氯 在 吡啶 、 4-二甲氨基吡啶 作用下， 以 氯仿 为溶剂， 反应 20.0h， 以97%的产率得到methyl 3-{bis[(4-methylnaphthalen-1-yl)carbonyl]amino}pyrazine-2-carboxylate
  参考文献：
  名称：

  Discovery of Agonists of Cannabinoid Receptor 1 with Restricted Central Nervous System Penetration Aimed for Treatment of Gastroesophageal Reflux Disease

  摘要：

  Agonists of the cannabinoid receptor 1 (CB1) have been suggested as possible treatments for a range of medical disorders including gastroesophageal reflux disease (GERD). While centrally acting cannabinoid agonists are known to produce psychotropic effects, it has been suggested that the CB1 receptors in the periphery could play a significant role in reducing reflux. A moderately potent and highly lipophilic series of 2-aminobenzamides was identified through focused screening of GPCR libraries. Development of this series focused on improving potency and efficacy at the CB1 receptor, reducing lipophilicity and limiting the central nervous system (CNS) exposure while maintaining good oral absorption. Improvement of the series led to compounds having excellent potency at the CB1 receptor and high levels of agonism, good physical and pharmacokinetic properties, and low penetration into the CNS. A range of compounds demonstrated a dose-dependent inhibition of transient lower esophageal sphincter relaxations in a dog model.

  DOI：

  10.1021/jm301511h

文献信息

• Discovery of Agonists of Cannabinoid Receptor 1 with Restricted Central Nervous System Penetration Aimed for Treatment of Gastroesophageal Reflux Disease
  作者：Alleyn T. Plowright、Karolina Nilsson、Madeleine Antonsson、Kosrat Amin、Johan Broddefalk、Jörgen Jensen、Anders Lehmann、Shujuan Jin、Stephane St-Onge、Mirosław J. Tomaszewski、Maxime Tremblay、Christopher Walpole、Zhongyong Wei、Hua Yang、Johan Ulander

  DOI：10.1021/jm301511h

  日期：2013.1.10

  Agonists of the cannabinoid receptor 1 (CB1) have been suggested as possible treatments for a range of medical disorders including gastroesophageal reflux disease (GERD). While centrally acting cannabinoid agonists are known to produce psychotropic effects, it has been suggested that the CB1 receptors in the periphery could play a significant role in reducing reflux. A moderately potent and highly lipophilic series of 2-aminobenzamides was identified through focused screening of GPCR libraries. Development of this series focused on improving potency and efficacy at the CB1 receptor, reducing lipophilicity and limiting the central nervous system (CNS) exposure while maintaining good oral absorption. Improvement of the series led to compounds having excellent potency at the CB1 receptor and high levels of agonism, good physical and pharmacokinetic properties, and low penetration into the CNS. A range of compounds demonstrated a dose-dependent inhibition of transient lower esophageal sphincter relaxations in a dog model.