Synthesis and physiological effects of new 4-aminophenol derivatives as paracetamol analogues

IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL
Maryna Lisouskaya , Olga A. Antipova , Irina P. Zhavoronok , Alexander Mikhalchuk
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引用次数: 0

Abstract

Paracetamol has antipyretic and analgesic properties and it is widely used for fever and pain. However, paracetamol is partially metabolized to N-acetyl-p-benzoquinoneimine, which in overdose leads to liver necrosis, urging for safer paracetamol analogues. As the latter, new para-aminophenol derivatives containing fragments of acetic acid, saturated fatty acids and monoethanolamine were synthesized. The obtained compounds at equimolar doses of paracetamol (0.5 mmol/kg) have been shown to have modulating effect on thermoregulatory (in experimental fever) and nociceptive (in experimental arthritis) reactions. The studied derivatives in rats with LPS-induced fever leveled the first phase of the febrile response and reduced the increase in core body temperature in the second phase by three times. The synthesized compounds in rats with zymosan-induced arthritis suppressed the nociceptive response in Randall–Selitto test and Hot plate test by 21–48 % and 8–42 %, respectively.

Abstract Image

新型4-氨基酚类扑热息痛类似物的合成及生理效应。
扑热息痛具有解热镇痛的特性,广泛用于发烧和疼痛。然而,扑热息痛部分代谢为n -乙酰基-对苯醌亚胺,过量会导致肝坏死,迫切需要更安全的扑热息痛类似物。合成了含有乙酸、饱和脂肪酸和单乙醇胺片段的对氨基酚衍生物。所获得的化合物在等摩尔剂量的扑热息痛(0.5 mmol/kg)已被证明对体温调节(在实验性发烧中)和伤害性(在实验性关节炎中)反应具有调节作用。lps诱导的发热大鼠的衍生物使第一阶段的发热反应保持平稳,并使第二阶段的核心体温升高降低三倍。在Randall-Selitto实验和Hot plate实验中,合成的化合物对大鼠关节炎损伤性反应的抑制作用分别为21- 48%和8- 42%。
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来源期刊
CiteScore
5.70
自引率
3.70%
发文量
463
审稿时长
27 days
期刊介绍: Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.
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