Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Strasse 9, D-60438 Frankfurt, Germany.
J Med Chem. 2011 Mar 24;54(6):1943-7. doi: 10.1021/jm101165z. Epub 2011 Feb 22.
A novel class of potent direct 5-lipoxygenase (5-LO) inhibitors bearing a thiazolinone-scaffold identified by virtual screening is presented. A range of substitutions and the importance of the 2-phenyl moiety were evaluated. This series is characterized by high potency in intact polymorphonuclear leukocytes and a cell-free system, exemplified by (Z)-2-(4-chlorophenyl)-5-(4-methoxybenzylidene)-5H-thiazol-4-one (18, IC(50) = 0.28 and 0.09 μM). These disubstituted thiazolinones may possess potential for intervention with inflammatory and allergic diseases and certain cancer types.
呈现了一类新型强效的直接 5-脂氧合酶（5-LO）抑制剂，这些抑制剂通过虚拟筛选得到，具有噻唑烷酮支架。评估了一系列取代基和 2-苯基部分的重要性。该系列在完整的多形核白细胞和无细胞系统中表现出高活性，（Z）-2-（4-氯苯基）-5-（4-甲氧基亚苄基）-5H-噻唑-4-酮（18，IC50 = 0.28 和 0.09 μM）就是一个例子。这些双取代噻唑烷酮可能具有干预炎症和过敏疾病以及某些癌症类型的潜力。
