2-(2-(4-(2-furoyl)piperazinyl)ethyl)-2,4-dihydro-7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2-(2-(4-(2-furoyl)piperazinyl)ethyl)-2,4-dihydro-7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazole
• 英文别名: Furan-2-yl-[4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)ethyl]piperazin-1-yl]methanone；furan-2-yl-[4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)ethyl]piperazin-1-yl]methanone
• 化学式: C₂₄H₂₈N₄O₄
• 分子量: 436.511
• InChiKey: AQWDNHQURKZWRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  73
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  7-甲氧基-2,2-二甲基苯并二氢吡喃-4-酮 在 sodium hydride 、 potassium carbonate 、 肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 7.18h， 生成 2-(2-(4-(2-furoyl)piperazinyl)ethyl)-2,4-dihydro-7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazole
  参考文献：
  名称：

  Identification of Novel GPR55 Modulators Using Cell-Impedance-Based Label-Free Technology

  摘要：

  The orphan G protein-coupled receptor GPR55 has been proposed as a novel receptor of the endocannabinoid system. However, the validity of this categorization is still under debate mainly because of the lack of potent and selective agonists and antagonists of GPR55. Binding assays are not yet available for GPR55 screening, and discrepancies in GPR55 mediated signaling pathways have been reported. In this context, we have designed and synthesized novel GPR55 ligands based on a chromenopyrazole scaffold. Appraisal of GPR55 activity was accomplished using a label-free cell-impedance-based hGPR55-HEK293 cells. The real-time impedance responses provided an integrative assessment of the cellular consequence GPR55 stimulation taking into account the different possible signaling pathways. Potent GPR55 partial agonists (14b, 18b, 19b, 20b, and 21-24) have been identified; one of them (14b) being selective versus classical cannabinoid receptors. Upon antagonist treatment, chromenopyrazoles 21-24 inhibited lysophosphatidylinositol (LPI) effect. One of these GPR55 antagonists (21) is fully selective versus classic cannabinoid receptors. Compared to LPI, the predicted physicochemical parameters of the new compounds suggest a clear pharmacokinetic improvement.

  DOI：

  10.1021/acs.jmedchem.5b01331

文献信息

• SELECTIVE MODULATORS OF THE ACTIVITY OF THE GPR55 RECEPTOR: CHROMENOPYRAZOLE DERIVATIVES
  申请人：Consejo Superior de Investigaciones Científicas (CSIC)

  公开号：EP3305794B1

  公开（公告）日：2020-02-05