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学科主题: 药学
题名:
A new class of analgesic agents toward prostacyclin receptor inhibition: Synthesis, biological studies and QSAR analysis of 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazolines
作者: Zhao, Ming2; Li, Zheng3; Peng, Li2; Tang, Yu-Rong1; Wang, Chao3; Zhang, Ziding1; Peng, Shiqi2
关键词: tetramethylimidazoline ; analgesic ; vasorelaxation ; QSAR
刊名: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
发表日期: 2008-05-01
DOI: 10.1016/j.ejmech.2007.07.007
卷: 43, 期:5, 页:1048-1058
收录类别: SCI ; IC
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Medicinal
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: FREE-RADICALS ; NITRONYL NITROXIDE ; VARIABLE SELECTION ; DERIVATIVES ; DISEASE ; DESCRIPTORS ; CYTOTOXICITY ; ANTIOXIDANTS ; CANCER
英文摘要:

By studying the structural similarity of analgesic imidazolines and 2-phenylnitronyl nitroxides, 20 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazolines (2a-t) were newly synthesized as selective antagonists of prostacyclin receptor (IP receptor). In the in vivo tail-flick assay, 2a-t (dose, 0.13 mmol/kg) receiving mice showed increased pain thresholds ranging from 20.52 +/- 7.25% to 90.94 +/- 11.97%, which were significantly higher than that ranged from 12.27 +/- 9.56% to 17.71 +/- 7.00% shown by normal saline (NS) receiving mice. In the in vivo tail bleeding assay, 2a-t (dose, 1.30 mmol/kg) receiving mice gave a bleeding time ranging from 116.3 +/- 8.0 s to 119.6 +/- 7.1 s, and NS receiving mice gave a bleeding time ranging from 116.7 +/- 7.5 s to 119.1 +/- 8.7 s, which were at a substantially equal level. These observations imply that no bleeding risk occurred even when 10-fold dose of analgesic assay was used. In the in vitro vasorelaxation assay, it was found that when the aortic strip contracted by noradrenaline (NE, final concentration, 10(-7) M) was treated with the solution of 2a-t in NS (final concentration, 5 x 10(-3) M) only lower percentage inhibitions ranged from 6.63 +/- 2.72% to 46.28 +/- 2.63% were recorded. Relatively higher concentration of 2a-t (5 x 10(-3) M) and relatively lower percentage inhibitions (13 of 20 less than 23.27 +/- 3.47%) suggest that 2a-t exhibit few vasodilation activity. To shed some light on the potential analgesic mechanisms of 2a-t, moreover, a QSAR analysis was carried out by using the multiple linear regression method. Taken altogether, the current study confirms that as selective antagonist of IP receptor 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazoline may be a promising lead compound of analgesic agent without cardiovascular and bleeding side effects. (C) 2007 Elsevier Masson SAS. All rights reserved.

语种: 英语
WOS记录号: WOS:000256570800017
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50053
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.China Agr Univ, Coll Biol Sci, Beijing 100094, Peoples R China
2.Capital Med Univ, Coll Pharmaceut Sci, Beijing 100069, Peoples R China
3.Peking Univ, Coll Pharmaceut Sci, Beijing 100083, Peoples R China

Recommended Citation:
Zhao, Ming,Li, Zheng,Peng, Li,et al. A new class of analgesic agents toward prostacyclin receptor inhibition: Synthesis, biological studies and QSAR analysis of 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazolines[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2008,43(5):1048-1058.
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