Department of Pharmaceutical/Medicinal Chemistry, Eberhard Karls University, Tübingen, Auf der Morgenstelle 8, D-72076 Tübingen, Germany.
J Med Chem. 2012 Oct 25;55(20):8958-62. doi: 10.1021/jm3010543. Epub 2012 Oct 9.
mPGES-1 is a promising target for development of new anti-inflammatory drugs. We aimed to create mPGES-1 inhibitors by modifying the structure of NSAIDs by replacing the carboxylic acid functionality by sulfonamide moieties. Compounds were also tested for 5-LOX inhibition. The most potent mPGES-1 inhibitor was lonazolac derivative 22 (IC₅₀ = 0.16 μM), while the best 5-LOX inhibition was attained by indomethacin derivative 17 (IC₅₀ = 0.9 μM). Inhibition of COX-1 activity was completely removed.
mPGES-1 是开发新型抗炎药物的有希望的靶点。我们旨在通过用磺酰胺取代 NSAIDs 的羧酸功能来改变 mPGES-1 的结构来创建 mPGES-1 抑制剂。还测试了化合物对 5-LOX 的抑制作用。最有效的 mPGES-1 抑制剂是 lonazolac 衍生物 22（IC₅₀ = 0.16 μM），而吲哚美辛衍生物 17（IC₅₀ = 0.9 μM）对 5-LOX 的抑制作用最好。COX-1 活性的抑制完全消除。
