4-取代-5-乙酰基-2-甲基-6-苯基-3(2H)哒嗪酮作为小鼠贴壁巨噬细胞中前列腺素E2和白细胞介素-1释放的抑制剂

4-substituted-5-acetyl-2-methyl-6-phenyl-3(2H)pyridazinones as PGE2 and IL-1 release inhibitors from mouse adherent macrophages.

作者信息

Dal Piaz V, Giovannoni M P, Ciciani G, Becherucci C, Parente L

机构信息

Dipartimento di Scienze Farmaceutiche, Università di Firenze, Italy.

出版信息

Pharmacol Res. 1994 May-Jun;29(4):367-72. doi: 10.1016/1043-6618(94)80058-8.

DOI:10.1016/1043-6618(94)80058-8

PMID:7971688

Abstract

A series of 4,5-functionalized 3(2H)-pyridazinones were evaluated as prostaglandin E2 (PGE2) and interleukin-1 (IL-1) release inhibitors from mouse adherent macrophages. Among the tested compounds only 2b was found to be devoid of activity in both the PGE2 and IL-1 tests, whereas the other compounds, showed a significant dose-dependent activity. Compounds 2a, 3 and 4 were able to inhibit PGE2 better than IL-1 release from stimulated macrophages. Compound 4, which showed an IC50 = 5.5 microM in the IL-1 test, appears to be a promising agent in this cell inflammation model. Structure-activity relationship (SAR) studies demonstrated the importance of the presence of a substituent characterized by a positive sigma constant at position 4 of the pyridazine system.

摘要

对一系列4,5-官能化的3(2H)-哒嗪酮作为小鼠贴壁巨噬细胞中前列腺素E2（PGE2）和白细胞介素-1（IL-1）释放抑制剂进行了评估。在测试的化合物中，仅发现2b在PGE2和IL-1测试中均无活性，而其他化合物表现出显著的剂量依赖性活性。化合物2a、3和4抑制PGE2的能力优于抑制刺激巨噬细胞释放IL-1的能力。化合物4在IL-1测试中显示IC50 = 5.5微摩尔，在该细胞炎症模型中似乎是一种有前景的药物。构效关系（SAR）研究表明，哒嗪系统4位上具有正σ常数特征的取代基的存在很重要。