1-苯基-3,6,6-三甲基-6,7-二氢-1氢-吲哚-4(5氢)-酮 | 21269-61-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1-苯基-3,6,6-三甲基-6,7-二氢-1氢-吲哚-4(5氢)-酮
• 英文名称: 1-phenyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydroindazole
• 英文别名: 1-phenyl-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one；1-Phenyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydroindazol；3,6,6-Trimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydroindazol；3,6,6-trimethyl-1-phenyl-1,5,6,7-tetrahydro-indazol-4-one；3,6,6-trimethyl-1-phenyl-1,5,6,7-tetrahydro-4H-indazol-4-one；3,6,6-Trimethyl-1-phenyl-1,5,6,7-tetrahydro-indazol-4-on；3,6,6-trimethyl-1-phenyl-6,7-dihydro-1H-indazol-4(5H)-one；3,6,6-trimethyl-1-phenyl-5,7-dihydroindazol-4-one
• CAS: 21269-61-4
• 化学式: C₁₆H₁₈N₂O
• 分子量: 254.332
• InChiKey: SMBNLMLYUWLSHO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-苯基-3,6,6-三甲基-6,7-二氢-1氢-吲哚-4(5氢)-酮 在 sodium tetrahydroborate 、 硫酸 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 16.0h， 生成 N-(3,6,6-trimethyl-1-phenyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)acrylamide
  参考文献：
  名称：

  A facile synthesis of 4-acylamino-tetrahydroindazoles via the Ritter reaction

  摘要：

  A new route toward 4-acylamino- and 4-amino-substituted tetrahydroindazoles is disclosed. The title compounds are obtained in good to excellent yields in the Ritter reaction between 4-hydroxy-tetrahydroindazoles and various nitriles. The reactivity of the tetrahydroindazole-derived carbenium ion is both sufficiently high to react with trichloroacetonitrile and sufficiently selective to resist the azide functionality within its structure. The present approach adds a method to the toolbox of tetrahydroindazole chemistry and facilitates the structural modifications of the scaffold, which has found important applications in medicinal chemistry. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2012.05.074
• 作为产物：
  描述：

  2-乙酰基-5,5-二甲基-1,3-环己二酮 在 乙醇 作用下， 生成 1-苯基-3,6,6-三甲基-6,7-二氢-1氢-吲哚-4(5氢)-酮
  参考文献：
  名称：

  Crossley; Renouf, Journal of the Chemical Society, 1912, vol. 101, p. 1536

  摘要：

  DOI：

文献信息

• 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
  作者：Ming-Fu Cheng、Li-Chin Ou、Shu-Chun Chen、Wan-Ting Chang、Ping-Yee Law、Horace H. Loh、Yu-Sheng Chao、Chuan Shih、Shiu-Hwa Yeh、Shau-Hua Ueng

  DOI：10.1016/j.bmc.2014.07.012

  日期：2014.9

  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.
• Fischer indolization of 1-aryl-4-oxo-4,5,6,7-tetrahydroindazoles
  作者：I. A. Strakova、A. Ya. Strakov、M. V. Petrova

  DOI：10.1007/bf02253233

  日期：1997.9
• 4, 5, 6, 7-TETRAHYDROINDAZOLE DERIVATIVES AS ANTITUMOR AGENTS
  申请人：Pharmacia Italia S.p.A.

  公开号：EP1177185B1

  公开（公告）日：2005-04-20
• OPIOID RECEPTOR MODULATORS AND USE THEREOF
  申请人：Regents of the University of Minnesota

  公开号：EP3344997B1

  公开（公告）日：2020-11-18
• US6716856B1
  申请人：——

  公开号：US6716856B1

  公开（公告）日：2004-04-06