1-(4-methoxyphenyl)-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydroindazole | 51300-52-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-methoxyphenyl)-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydroindazole
• 英文别名: 1-(4-methoxyphenyl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one；3,6,6-Trimethyl-4-oxo-1-(p-methoxyphenyl)-4,5,6,7-tetrahydroindazol；1-(4-methoxy-phenyl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indazol-4-one；1-(4-Methoxyphenyl)-3,6,6-trimethyl-5,7-dihydroindazol-4-one
• CAS: 51300-52-8
• 化学式: C₁₇H₂₀N₂O₂
• 分子量: 284.358
• InChiKey: SIEMMYUIIJKHLU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-乙酰基-5,5-二甲基-1,3-环己二酮 、 4-甲氧基苯肼盐酸盐 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 5.0h， 以40%的产率得到1-(4-methoxyphenyl)-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydroindazole
  参考文献：
  名称：

  Discovery, structure–activity relationship studies, and anti-nociceptive effects of 1-phenyl-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one as novel opioid receptor agonists

  摘要：

  The μ-opioid receptor (MOR) is the major opioid receptor targeted by most analgesics in clinical use. However, the use of all known MOR agonists is associated with severe adverse effects. We reported that the 1-phenyl-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-ones are novel opioid receptor agonists. Subsequent structural modification resulted in the potent MOR/KOR (κ-opioid receptor) agonists 19, 20, and 21. Testing the analgesic effect of these in WT B6 mice (tail-flick test) gave ED50 values of 8.4, 10.9, and 26.6mg/kg, respectively. The 1-phenyl-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one core could be addressed in 1 or 2 synthetic steps with moderate to high percent of yield. In the adenylyl cyclase assay, compound 19 displayed a MOR/KOR agonist profile, with IC50 values of 0.73 and 0.41μM, respectively. Current results suggest that compound 19 is a promising lead to go further development and in vitro/in vivo adverse effects studies.

  DOI：

  10.1016/j.bmc.2014.07.012

文献信息

• 1-(1-Phthalazinyl)- and 1-(4methoxyphenyl)-6,6dimethyl-4oxo-4,5,6,7-tetrahydroindazole
  作者：A. Ya. Strakov、I. A. Strakova、M. V. Petrova

  DOI：10.1007/bf01164795

  日期：1996.5