Inhibition of homodimerization of Toll-like receptor 4 by 4-oxo-4-(2-oxo-oxazolidin-3-yl)-but-2-enoic acid ethyl ester

Toll-like receptor 4 signaling in intracerebral hemorrhage-induced inflammation and injury

“…Some antagonists, such as curumin, 6-shogaol, isoliquiritigenin, and OSL07 (4-oxo-4-(2-oxo-oxazolidin-3-yl)-but-2-enoic acid ethyl ester), block TLR4 signaling by inhibiting homodimerization of TLR4 [96-99]. Other agents, such as sparstolonin B, auranofin, TAK-242, and M62812, have also been reported to block TLR4 signaling pathways selectively [100-103].…”

Development of β-Amino Alcohol Derivatives That Inhibit Toll-like Receptor 4 Mediated Inflammatory Response as Potential Antiseptics

“…To the best of our knowledge, none have successfully advanced through late stage clinical trials. 16,17,18 TAK-242 (resatorvid), the most successful TLR4-binding small molecule antagonist, reached Phase III clinical trials as an antisepsis agent but studies were recently discontinued due to a failure to suppress cytokine levels in patients despite showing promising preclinical efficacy in animal models. 19–21 These results might suggest that the current approaches to targeting the TLR4 receptor are flawed.…”

“…An alternative strategy, which has the potential for high specificity and bioavailability, is to design low-molecular-weight inhibitors. , By use of this strategy, several small molecules have been developed to target and antagonize TLR4. To the best of our knowledge, none have successfully advanced through late stage clinical trials. − TAK-242 (resatorvid), the most successful TLR4-binding small molecule antagonist, reached phase III clinical trials as an antisepsis agent, but studies were recently discontinued because of a failure to suppress cytokine levels in patients despite showing promising preclinical efficacy in animal models. − These results might suggest that the current approaches to targeting the TLR4 receptor are flawed. There is an urgent need to develop and validate novel strategies to target the TLR4 pathway for antisepsis therapeutic development.…”

Oxazolidinones as versatile scaffolds in medicinal chemistry

“…Furthermore, compound 89 was active in a mouse model of peritoneal inflammation (a known model in which LT is known to play an essential role), significantly reducing the LTC 4 content of the lavage fluid. 136 Oxazolidinones have also been investigated as inhibitors of the toll-like receptor 4 (TLR4), 138 a critical receptor involved in many inflammatory responses, such as LPS recognition. 139 Oxazolidinone 90 ( Fig.…”