Discovery and optimization of 4-oxo-2-thioxo-thiazolidinones as NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inhibitors.

Discovery and optimization of 4-oxo-2-thioxo-thiazolidinones as NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inhibitors.
Bioorg Med Chem Lett. 2020 Feb 06;:127021
Authors: Chen Y, He H, Jiang H, Li L, Hu Z, Huang H, Xu Q, Zhou R, Deng X
Abstract
Aberrant activation of NLRP3 inflammasome is present in a subset of acute and chronic inflammatory diseases. The NLRP3 inflammasome has been recognized as an attractive therapeutic target for developing novel and specific anti-inflammatory inhibitors. Cellular structure-activity relationship-guided optimization resulted in the identification of 4-oxo-2-thioxo-thiazolidinone derivative 9 as a selective and direct small-molecule inhibitor of NLRP3 with IC50 of 2.4 μM, possessing favorable ex vivo and in vivo pharmacokinetic properties. Compound 9 may represent a lead for the development of anti-inflammatory therapeutics for treating NLRP3-driven diseases.
PMID: 32057583 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry Letters - February 5, 2020 Category: Chemistry Authors: Chen Y, He H, Jiang H, Li L, Hu Z, Huang H, Xu Q, Zhou R, Deng X Tags: Bioorg Med Chem Lett Source Type: research