24044-44-8

Upstream product

• 21346-21-4 3-(4-hydroxyphenyl)-2-thioxothiazolidin-4-one 
• 2153-11-9 4-chloroacetamidophenol 
• 57628-39-4 3-(4-hydroxy-phenyl)-2-(4-iodo-phenylimino)-thiazolidin-4-one 

Downstream Products

• 73219-69-9 (4-hydroxy-phenyl)-thiazolidinetrione 5-(naphthalen-2-yl-hydrazone) 
• 73282-64-1 4-{[3-(4-hydroxy-phenyl)-2,4-dioxo-thiazolidin-5-ylidene]-hydrazino}-benzenesulfonamide 
• 51964-11-5 3-(4-hydroxy-phenyl)-5-(2-oxo-1,2-dihydro-indol-3-ylidene)-thiazolidine-2,4-dione 

Relevant academic research and scientific papers

Thiazolidine-2,4-dione-based irreversible allosteric IKK-β kinase inhibitors: Optimization into in vivo active anti-inflammatory agents

Selective kinase inhibitors development is a cumbersome task because of ATP binding sites similarities across kinases. On contrast, irreversible allosteric covalent inhibition offers opportunity to develop novel selective kinase inhibitors. Previously, we

NIFUROXAZIDE ANALOGS AND THERAPEUTIC USES THEREOF

Nifuroxazide analogs, and their pharmaceutically acceptable salts and derivatives are described. Methods and uses are also provided that include the administration of an effective amount of the nifuroxazide analogs, or their pharmaceutically acceptable sa

Optimization study towards more potent thiazolidine-2,4-dione IKK-β modulator: Synthesis, biological evaluation and in silico docking simulation

Inhibition of IKK-β (inhibitor of nuclear factor kappa-B kinase subunit beta) has been broadly documented as a promising approach for treatment of acute and chronic inflammatory diseases, cancer, and autoimmune diseases. Recently, we have identified a novel class of thiazolidine-2,4-diones as structurally novel modulators for IKK-β. Herein, we report a hit optimization study via analog synthesis strategy aiming to acquire more potent derivative(s), probe the structure activity relationship (SAR), and get reasonable explanations for the elicited IKK-β inhibitory activities though an in silico docking simulation study. Accordingly, a new series of eighteen thiazolidine-2,4-dione derivatives was rationally designed, synthesized, identified with different spectroscopic techniques and biologically evaluated as noteworthy IKK-β potential modulators. Successfully, new IKK-β potent modulators were obtained, including the most potent analog up-to-date 7m with IC50 value of 260 nM. A detailed structure activity relationship (SAR) was discussed and a mechanistic study for 7m was carried out indicating its irreversible inhibition mode with IKK-β (Kinact value = 0.01 (min?1). Furthermore, the conducted in silico simulation study provided new insights for the binding modes of this novel class of modulators with IKK-β.

Design, synthesis and biological evaluation of novel thiazolidinedione derivatives as irreversible allosteric IKK-β modulators

The kinase known as IKK-β activates NF-κB signaling pathway leading to expression of several genes contributing to inflammation, immune response, and cell proliferation. Modulation of IKK-β kinase activity could be useful for treatment and management of such diseases. Starting from a discovered weakly active hit compound, twenty four thiazolidinedione-scaffold based chemical entities belonging to five series have been designed, synthesized and evaluated as potential IKK-β modulators. Among them, compounds 6q, 6r and 6u showed low micromolar IC50 values while compounds 6v, 6w, and 6x elicited submicromolar IC50 values equal to 0.4, 0.7 and 0.9 μM respectively. These submicromolar IC50 values are 243, 139 and 105 folds the value of the reported IC50 of the starting hit compound. Kinetic study of compounds 6v and 6w confirmed this class of modulators as irreversible inhibitors. LPS-treated RAW 264.7 macrophages proved the anti-inflammatory activity of compounds 6q and 6v. Assay of hERG inhibition demonstrated a safe profile of compound 6q suggesting it as a lead for further development of IKK-β modulators.