2.4- Thiazolidinedione

Diazo coupling is expected to occur only with highly reactive systems, and experiment bears this out. Diazonium ions couple with the anions of N-unsubstituted imidazoles at the 2-position (e.g. 125 yields 126) and with indazoles (127) in the 3-position. In general, other azoles react only when they contain an amino, hydroxyl, or potential hydroxyl group, e.g. the 4-hydroxypyrazole (128), the triazolinone (129) and the thiazolidinedione (130) (all these reactions occur on the corresponding anions). 

The thiazolidinediones have also been reported to act as inhibitors of the respiratory chain at high concentrations, and this appears to account for their ability to activate AMGPK in cultured cells. However, the primary target of the thiazolidinediones appears to be the peroxisome proliferator-activated receptor-y ( PPAR-y), a member of the nuclear receptor superfamily expressed in adipocytes. One of the major effects of stimulation of PPAR-y in adipocytes is the release ofthe... 

Thiazolidinediones Pioglitazone, rosiglitazone Improve insulin action (PPARy agonists) Oral... 

Synthetic ligands Thiazolidinediones and some non-steroidal antiinflammatory drugs... 

Thiazolidinediones Cardiac failure liver disease Oedema, anaemia, heart failure, fractures in women LFTb... 

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 . 

Thiazolidinediones (synonyms glitazones, insulin sensitizers rosiglitazone, pioglitazone) are a novel class of oral antidiabetic drugs that activate the transcription factor peroxisome proliferator-activated receptor (PPARy). Thiazolidinediones ameliorate insulin resistance in obese animal models and in individuals... 

Finally, it has to be mentioned that LPA also has an intracellular target site, which is the nuclear transcription factor, peroxisome proliferator-activated receptor-y (PPARy). LPA competes for thiazolidinedione binding and activates PPARy-dependent gene transcription. Thereby, LPA induced neointima formation in a rat carotid artery model. 

PPARy NR1C3 Fatty acids, prostaglandin J2, thiazolidinediones... 

A nuclear receptor that is a key transcription factor in adipocytes. It plays a critical role in the control of adipocyte differentiation and is involved in the regulation of the expression of specific adipokines, including leptin and adiponectin. It has anti-inflammatory actions and is the target of the thiazolidinedione drugs. The preintegration complex is a complex of retroviral DNA and proteins that translocates from the cytosol into the nucleus prior to integration. Gene Therapy... 

The synchronised oscillatory activity between the intrinsically linked thalamus and cortex. Under normal circumstances there is a level of activity which changes during the sleep-wake cycle increasing during periods of slow wave sleep. Excess synchrony occurs in conditions such as epilepsy. Thiazolidinedione... 

THIAZOLIDINEDIONES. The thiazolidinediones, piogli-tazone and rosiglitazone, are given with or without meals. If the dose is missed at the usual meal, the drug is taken at the next meal. If the dose is missed on one day, do not double the dose the following day. If the drug is taken, do not delay the meal. Delay of a meal for as little as y2 hour can cause hypoglycemia. 

CN ( )-5-[[4-[2-(5-Ethyl-2-pyridinyl)ethoxy]phenyl]methyI]-2,4-thiazolidinedione hydrochloride... 

CN 5-[[4-(3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2//-l-benzopyran-2-yl)methoxy]pheny ]methyl-2,4-thiazolidinedione... 

C4H3NO2S 397S-08-8) see Tiabendazole (/ )-4-thiazoIidinecarboxylic acid (C4H,N02S J4592-47-7) see Telmesteine 2,4-thiazolidinedione... 

Kassahun, K. Pearson, P. G. Tang, W. McIntosh, I. Leung, K. Elmore, C. Dean, D. Wang, R. Doss, G. Baillie, T. A. Studies on the metabolism of troglitazone to reactive intermediates in vitro and in vivo. Evidence for novel biotransformation pathways involving quinone methide formation and thiazolidinedione ring scission. Chem. Res. Toxicol. 2001, 14, 62-70. 

Uncontrolled hypertension Valvular disorders function sympathomi meti cs) Offending medications (NSAIDs, COX-2 inhibitors, steroids, lithium, (i-blockers, calcium channel blockers, anti-arrhythmics, alcohol, thiazolidinediones)... 

Metformin also has been shown to produce beneficial effects on serum lipid levels and thus has become a first-line agent for type 2 DM patients with metabolic syndrome. Triglyceride and low-density lipoprotein (LDL) cholesterol levels often are reduced by 8% to 15%, whereas high-density lipoprotein (HDL) cholesterol improves by approximately 2%. A modest weight loss of 2 to 3 kg (4.4—6.6 lb) also has been reported with metformin therapy. Metformin often is used in combination with a sulfonylurea or a thiazolidinedione for synergistic effects. 

FPG levels by 30 to 50 mg/dL (1.67-2.78 mmol/L), and the overall effect on HbAlc is a 1% to 1.5% reduction. Onset of action for thiazolidinediones is delayed for several weeks and may require up to 12 weeks before maximum effects are observed. Combining a sulfonylurea, non-sulfonylurea secret-agogue, metformin, or insulin with a thiazolidinedione can improve HbAlc reductions to 2% to 2.5%. 

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