作为新型沙利度胺类似物设计的邻苯二甲酰亚胺衍生物的合成及抗炎活性
Synthesis and anti-inflammatory activity of phthalimide derivatives, designed as new thalidomide analogues.
作者信息
Lima Lídia M, Castro Paulo, Machado Alexandre L, Fraga Carlos Alberto M, Lugnier Claire, de Moraes Vera Lúcia Gonçalves, Barreiro Eliezer J
机构信息
Laboratório de Avaliação e Síntese de Substâncias Bioativas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Brazil.
出版信息
Bioorg Med Chem. 2002 Sep;10(9):3067-73. doi: 10.1016/s0968-0896(02)00152-9.
This paper describes the synthesis and anti-inflammatory activity of new N-phenyl-phthalimide sulfonamides (3a-e) and the isosters N-phenyl-phthalimide amides (4a-e), designed as hybrids of thalidomide (1) and aryl sulfonamide phosphodiesterase inhibitor (2). In these series, compound 3e (LASSBio 468), having a sulfonyl-thiomorpholine moiety, showed potent inhibitory activity on LPS-induced neutrophil recruitment with ED(50)=2.5mg kg(-1), which was correlated with its inhibitory effect on TNF-alpha level.
本文描述了新型N-苯基-邻苯二甲酰亚胺磺酰胺（3a-e）及其电子等排体N-苯基-邻苯二甲酰亚胺酰胺（4a-e）的合成与抗炎活性，它们被设计为沙利度胺（1）与芳基磺酰胺磷酸二酯酶抑制剂（2）的杂合物。在这些系列化合物中，具有磺酰基-硫代吗啉部分的化合物3e（LASSBio 468）对脂多糖诱导的中性粒细胞募集表现出强效抑制活性，半数有效剂量（ED50）为2.5mg kg-1，这与其对肿瘤坏死因子-α水平的抑制作用相关。
Zotero 插件