Discovery of 3-(Indol-5-yl)-indazole Derivatives as Novel Myeloid Differentiation Protein 2/Toll-like Receptor 4 Antagonists for Treatment of Acute Lung Injury

values of 0.89 and 0.53 μM, respectively. Compound 22m was then identified as an MD2-TLR4 antagonist in suppressing LPS-induced inflammatory responses. In vivo administration of 22m significantly inhibited macrophage infiltration and ameliorated histopathological changes in lung tissues of LPS-challenged mice. Our studies have identified a new 3-(indol-5-yl)-indazole, 22m, as a potent MD2-TLR4 inhibitor and lay the groundwork for future drug development of anti-inflammatory agents for the treatment of ALI.