Peroxisome proliferator-activated receptor PPARy agonists

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). 

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 . 

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%). ... 

Peroxisome proliferator-activated receptor agonists PPARa agonist Ciglitazone Pioglitazone PPARy agonists WY 14.643... 

The activation of the retinoid X receptor, which dimerizes with peroxisome proliferator-activated receptors (PPARs), leads to an enhanced clearance of A(f from the brain of a transgenic mouse model of AD, with increased expression of ApoE and its main transporters. Both a PPARy agonist (ciplitazone) and a PPARa agonist (WT 14.643) are able to protect neurons by modulating mitochondrial fusion and fission, leading to a better response of neurons to oxidative stress, suggesting that a PPAR-based therapy could act simultaneously in different cellular components [437]. 

Burgermeister, E., Schnoebelen, A., Flament, A. et al. (2006) A novel partial agonist of peroxisome proliferator-activated receptor-y (PPARy) recruits PPARy-coactivator-la, prevents triglyceride accumulation, and potentiates insulin signaling in vitro. Molecular Endocrinology, 20, 809-830. 

Qin, C., Morrow, D., Stewart, J., Spencer, K., Porter, W., Smith, R., Ill, Phillips, T., Abdelrahim, M., Samudio, I. and Safe, S. (2004) A new class of peroxisome proliferator-activated receptor y (PPARy) agonists that inhibit growth of breast cancer cells l,l-bis(3 -indolyl)-l-(p-substituted phenyljmethanes. Molecular Cancer Therapeutics, 3, 247-259. 

Non-insulin-dependent diabetes mellitus (NIDDM) based thiazolidine-dione peroxisome proliferator activated receptors gamma (PPARy) agonists 13MRM706. 

---