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布洛芬酰胺衍生物的镇痛与抗炎活性的合成及研究

Synthesis and Study of Analgesic and Anti-inflammatory Activities of Amide Derivatives of Ibuprofen.

作者信息

Ahmadi Abbas, Khalili Mohsen, Olama Zahra, Karami Shirin, Nahri-Niknafs Babak

机构信息

Department of Medicinal Chemistry, Faculty of Science, Islamic Azad University, P.O. Box: 31485- 313, Karaj, Iran.

Neurophysiology Research Center, Shahed University, Tehran, Iran.

出版信息

Mini Rev Med Chem. 2017;17(9):799-804. doi: 10.2174/1389557516666161226155951.

Abstract

UNLABELLED

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs worldwide and represent a mainstay in the therapy of acute and chronic pain and inflammation. The traditional NSAIDs like ibuprofen (I) contain free carboxylic acid group which can produce gastrointestinal (GI) damage for long-term use.

OBJECTIVE

In order to obtain the novel NSAIDs with less side effects; carboxylic acid moiety has been modified into various amide groups which is the most active area of research in this family.

METHOD

In this research, synthesis of various pharmacological heterocyclic amides of ibuprofen is described. All the new compounds were tested for their analgesic and anti-inflammatory activities in mice and compared with standard (Ibuprofen) and control (saline) groups.

RESULTS & CONCLUSION: The results revealed that all the synthesized compounds (III-VI) exhibited more analgesic and anti-inflammatory activities in tail immersion (as a model of acute thermal pain), formalin (as a model of acute chemical and chronic pain) and paw edema (as a model of acute inflammation) tests when compared with standard and control animals. These pharmacological activities were significant for VI compared to other new compounds (III-V) which may be concern to more effective role of morpholin for the reduction of pain and inflammation compared to other used heterocyclic amines.

摘要

未标记

非甾体抗炎药(NSAIDs)是全球使用最广泛的药物之一,是治疗急慢性疼痛和炎症的主要药物。像布洛芬(I)这样的传统非甾体抗炎药含有游离羧酸基团,长期使用会对胃肠道(GI)造成损害。

目的

为了获得副作用较小的新型非甾体抗炎药;羧酸部分已被修饰成各种酰胺基团,这是该家族中最活跃的研究领域。

方法

本研究描述了布洛芬各种药理活性杂环酰胺的合成。所有新化合物均在小鼠中测试其镇痛和抗炎活性,并与标准组(布洛芬)和对照组(生理盐水)进行比较。

结果与结论

结果显示,与标准组和对照组动物相比,所有合成化合物(III - VI)在尾浸法(作为急性热痛模型)、福尔马林试验(作为急性化学性和慢性疼痛模型)和爪肿胀试验(作为急性炎症模型)中均表现出更强的镇痛和抗炎活性。与其他新化合物(III - V)相比,化合物VI的这些药理活性更为显著,这可能与吗啉相比于其他使用的杂环胺在减轻疼痛和炎症方面发挥更有效的作用有关。

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