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学科主题: 药学
题名:
Novel 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazolines: Synthesis, selectively analgesic action, and QSAR analysis
作者: Zhao, Ming; Li, Zheng; Peng, Li; Tang, Yu-Rong; Wang, Chao; Zhang, Ziding; Peng, Shiqi
关键词: tetramethylimidazoline ; analgesic ; vasorelaxation ; QSAR
刊名: BIOORGANIC & MEDICINAL CHEMISTRY
发表日期: 2007-04-15
DOI: 10.1016/j.bmc.2007.02.023
卷: 15, 期:8, 页:2815-2826
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Chemistry, Organic
研究领域[WOS]: Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
关键词[WOS]: ADRENERGIC-RECEPTORS ; ANTAGONISTS ; POTENT ; IMIDAZOLINES ; DERIVATIVES ; AGONISTS ; ANALOGS ; RATS ; MICE ; SAR
英文摘要:

Based on the knowledge that imidazoline can result in analgesic action due to its selective binding with the prostacyclin receptor, 20 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazolines (3a-t) were prepared in moderate yields. At 0.13 mmol/kg dose, their in vivo analgesic activities were evaluated after the mice were administered at 30, 60, 90, and 150 min. Compared with the pain threshold (12.27 +/- 9.56-17.71 +/- 7.00%) of normal saline (NS) receiving mice, the pain threshold (23.42 +/- 8.14% to 102.58 +/- 10.66%) of 3a-t receiving mice increases significantly. Considering a prostacyclin receptor targeting analgesic agent usually had bleeding action and to appraise the bleeding risk, the in vivo tail bleeding time of 1.30 mmol/kg 3a-t receiving mice was found to be ranged from 116.3 +/- 8.2 s to 120.3 +/- 9.2 s, which was substantially equal to that (117.8 +/- 8.4 s to 119.0 +/- 8.6 s) of NS receiving mice. Based on the possibility of imidazoline acting as vasodilator, the in vitro vasorelaxations of 3a-t were tested using the rat aortic strip model. When the aortic strip contracted by noradrenaline (NE, final concentration 10(-7) mol/l) was treated with 3a-t (final concentration 5 x 10(-4) mol/l), only lower percentage inhibitions (6.55 +/- 5.70-37.40 +/- 4.07%) were recorded, implying that the vasorelaxation of 3a-t was neglectable. By selecting appropriate molecular descriptors generated from e-dragon server, the QSAR model of the analgesic activities of 3a-t was constructed using the multiple linear regression method. The established QSAR model showed reasonable accuracy and thus it is promising to be used for screening new 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazoline derivatives as analgesic agents. (c) 2007 Elsevier Ltd. All rights reserved.

语种: 英语
WOS记录号: WOS:000245637200002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/68178
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Capital Med Univ, Coll Pharmaceut Sci, Beijing 100054, Peoples R China
2.Peking Univ, Coll Pharmaceut Sci, Beijing 100083, Peoples R China
3.China Agr Univ, Coll Biol Sci, Beijing 100094, Peoples R China

Recommended Citation:
Zhao, Ming,Li, Zheng,Peng, Li,et al. Novel 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazolines: Synthesis, selectively analgesic action, and QSAR analysis[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2007,15(8):2815-2826.
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