Institute of Pharmaceutical Chemistry, ZAFES/LiFF/OSF Goethe-University Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany.
Bioorg Med Chem. 2012 Jun 1;20(11):3575-83. doi: 10.1016/j.bmc.2012.04.003. Epub 2012 Apr 11.
A class of 5-lipoxygenase (5-LO) inhibitors characterized by a central 5-benzylidene-2-phenyl-thiazolinone scaffold was synthesized as a new series of molecular modifications and extensions of a previously reported series. Compounds were tested in a cell-based and a cell-free assay and furthermore evaluated for their influence on cell viability. The presented substituted thiazolinone scaffold turned out to be essential for both the 5-LO inhibitory activity and the non-cytotoxic profile. With (Z)-5-(4-methoxybenzylidene)-2-(naphthalen-2-yl)-5H-thiazol-4-one (2k, ST1237), a potent, direct, non-cytotoxic 5-LO inhibitor with IC(50) of 0.08 μM and 0.12 μM (cell-free assay and intact cells), we present a promising lead optimization and development for further investigations as novel anti-inflammatory drug.
一类 5-脂氧合酶（5-LO）抑制剂，其特征在于中心 5-亚苄基-2-苯基-噻唑啉酮骨架，作为先前报道的系列的新的分子修饰和扩展。将化合物在基于细胞的测定法和无细胞测定法中进行测试，并进一步评估它们对细胞活力的影响。所呈现的取代噻唑啉酮骨架对于 5-LO 抑制活性和非细胞毒性特征都是必不可少的。（Z）-5-（4-甲氧基亚苄基）-2-（萘-2-基）-5H-噻唑-4-酮（2k，ST1237）是一种有效的、直接的、非细胞毒性的 5-LO 抑制剂，其 IC50 为 0.08 μM 和 0.12 μM（无细胞测定法和完整细胞），我们提出了一种有前途的先导优化和开发，以进一步研究作为新型抗炎药物。
