Peroxisome proliferator-activated receptor agonists thiazolidinediones

Thiazolidinediones (Gamma-PPAR (peroxisome proliferator-activated receptor) agonists) Pioglitazone, Rosiglitazone... 

Thiazolidinediones (PPARy-agonists) Thiazolidine-diones ( pioglitazone, rosiglitazone) lower blood glucose levels in animal models of insulin resistance and also in insulin resistant patients. They are agonists of the peroxisome proliferator-activated receptor y (PPARy). Because they enhance the effect of insulin and reduce serum insulin levels in insulin resistant patients, thiazolidinediones are usually referred to as insulin sensitizers . 

Park, S. W., Yi, J. H., Miranpuri, G., Satriotomo, I., Bowen, K., Resnick, D. K., and Vemuganti, R. (2007). Thiazolidinedione class of peroxisome proliferator-activated receptor gamma agonists prevents neuronal damage, motor dysfunction, myelin loss, neuropathic pain, and inflammation after spinal cord injury in adult rats. J. Pharmacol. Exp. Ther. 320, 1002—1012. 

Rosiglitazone 9, an agonist of peroxisome proliferator activated receptor-y (PPARy), is a recently introduced antihyperglycemic thiazolidinedione effective in the treatment of noninsulin dependant diabetes mellitus (type II diabetes). A seven-step synthesis was developed (Scheme 3), which utilised supported reagents in combination with in-line SPE purifications. The introduction of the pyridine moiety provided a convenient molecular handle by which to purify the molecule throughout the synthesis. Notably, the overall yield (46%) for this synthesis was higher than the yield reported in the initial shorter solution-phase synthesis (31%). ... 

Thiazolidinediones are another class of heterocyclic carboxylic acid surrogates commonly used for peroxisome proliferator-activated receptors (PPAR) agonists, as potent antihyperglycemic and lipid activity modulators. Other interesting, but less studied heterocyclic surrogates are 3,5-dioxo-l,2,4-oxadiazohdine, 3-hydroxy-1,2,5-thiadiazoles, l,2,4-oxadiazole-5(4//)-ones, 1,2,4-thiadi-azole-5(4H)-ones , 3,5-difluoro-4-hydroxyphenyl, and 3 -hydroxy-7-pyrones. ... 

Synthetic peroxisome proliferator-activated receptors (PPARs) agonist in clinical use such as thiazolidinediones (TZDs) may limit inflammatory response (194). Also, PPARy, but not PPARa, activators repress interferon-y-induced MHC-II expression and subsequent inhibition of T-lymphocyte activation in atheroma-associated cells (195). 

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