3,5-dimethoxy-N'-(2-naphthalen-1-ylacetyl)benzohydrazide | 1004375-56-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3,5-dimethoxy-N'-(2-naphthalen-1-ylacetyl)benzohydrazide
• CAS: 1004375-56-7
• 化学式: C₂₁H₂₀N₂O₄
• 分子量: 364.401
• InChiKey: RYUWQMAWGNKHEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-萘乙酸 在 氯化亚砜 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 3,5-dimethoxy-N'-(2-naphthalen-1-ylacetyl)benzohydrazide
  参考文献：
  名称：

  Discovery and SAR of a Series of Agonists at Orphan G Protein-Coupled Receptor 139

  摘要：

  GPR139 is an orphan G-protein coupled receptor (GPCR) Which is primarily expressed in the central nervous system (CNS). In order to explore the biological function of this receptor, selective tool compounds are required. A screening campaign identified compound 1a as a high potency PR139 agonist with an EC(50) = 39 nM in a calcium mobilization assay in CHO-K1 cells stably expressing the GPR139 receptor. In the absence of a known endogenous ligand, the maximum effect was set as 100% for 1a. Screening against 90 diverse targets revealed no cross-reactivity issues. Assessment of the pharmacokinetic properties showed limited utility,as in vivo tool compound in rat with a poor whole brain exposure of 61 ng/g and a brain/plasma (b/p) ratio of 0.03. Attempts to identify a more suitable analogue identified the des-nitrogen analogue is with a reduced polar surface area of 76.7 angstrom(2) and an improved b/p ratio of 2.8. The whole brain exposure remained low at 95 ng/g due to a low plasma exposure.

  DOI：

  10.1021/ml100293q

文献信息

• Discovery and SAR of a Series of Agonists at Orphan G Protein-Coupled Receptor 139
  作者：Feng Shi、Jing Kang Shen、Danqi Chen、Karina Fog、Kenneth Thirstrup、Morten Hentzer、Jens-Jakob Karlsson、Veena Menon、Kenneth A. Jones、Kelli E. Smith、Garrick Smith

  DOI：10.1021/ml100293q

  日期：2011.4.14

  GPR139 is an orphan G-protein coupled receptor (GPCR) Which is primarily expressed in the central nervous system (CNS). In order to explore the biological function of this receptor, selective tool compounds are required. A screening campaign identified compound 1a as a high potency PR139 agonist with an EC(50) = 39 nM in a calcium mobilization assay in CHO-K1 cells stably expressing the GPR139 receptor. In the absence of a known endogenous ligand, the maximum effect was set as 100% for 1a. Screening against 90 diverse targets revealed no cross-reactivity issues. Assessment of the pharmacokinetic properties showed limited utility,as in vivo tool compound in rat with a poor whole brain exposure of 61 ng/g and a brain/plasma (b/p) ratio of 0.03. Attempts to identify a more suitable analogue identified the des-nitrogen analogue is with a reduced polar surface area of 76.7 angstrom(2) and an improved b/p ratio of 2.8. The whole brain exposure remained low at 95 ng/g due to a low plasma exposure.