From 2,4-Thiazolidinediones

A novel and efficient synthesis of 5-(hydroxymethyl)thiazole starting from 2,4-thiazolidinedione was performed with phosphorus oxybromide and DMF to give 2,4-dibromo-5-thiazolecarboxaldehyde in 72 % yield. Reduction of the aldehyde with NaBH4 and catalytic hydrogenation with Pd/C at room temperature afforded the desired product in excellent yield. [95SC2639]... 

Left two representatives of two groups of orally applied anti-diabetic drugs. Compound 1 derives from sulfonylurea and 2 from thiazolidinedione. Right schematic drawing of the hormone insulin. The active form, a monomer (shown), consists of two peptide chains which are hnked by two disulfide bridges. Chain A contains an additional disulfide hnk. 

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 answer is c. (Katzung, p 729.) Hepatic dysfunction has occurred particularly with the use of troglitazone, necessitating its removal from the market Patients treated with other thiazolidinediones should be monitored for this possibility... 

Isocyanates can be formed by oxidative dehydrogenation (see Oxidative Dehydrogenation section and Figure 4.71 in Chapter 4). Isocyanates can also be formed from the oxidation of sulfonylureas (e.g., tolbutamide) (29) and thiazolidinediones (e.g., trogli-tazone) (30), as shown in Figure 8.19. Both of these classes of drugs are used to treat... 

In summary, results from several studies in to the effects of impaired insulin action can now be linked to CVD. Because of the numbers of people exhibiting sings of insulin resistance, there has been a lot of research effort has gone in to finding suitable therapeutic interventions. One group of drugs in particular, the thiazolidinediones (also known as glitazones) has attracted attention because they both increase insulin sensitivity and help to normalize plasma lipid concentrations. 

Nesto RW, Bell D, Bonow RO, et al. Thiazolidinedione use, fluid retention, and congestive heart failure a consensus statement from the American Heart Association and American Diabetes Association. October 7, 2003. Circulation. Dec 9 2003 108(23) 2941-2948. 

The members of this class are derivatives of the parent compound thiazolidinedione, and include rosiglitazone, pioglitazone and troglitazone which was withdrawn from the market due to an increased incidence of drug-induced hepatitis. 

Two thiazolidinediones are currently available pioglitazone and rosiglitazone (Table 41-8). Their distinct side chains create differences in therapeutic action, metabolism, metabolite profile, and adverse effects. An earlier compound, troglitazone, was withdrawn from the market because of hepatic toxicity thought to be related to its side chain. 

The different mechanisms of action of the various classes of hypoglycemic drugs makes combined therapy feasible the sulfonylureas and meglitinides stimulate insulin production by different mechanisms, the biguanides reduce glucose production by the liver and excretion from the liver, acarbose reduces the absorption of glucose from the gut, and the thiazolidinediones reduce insulin resistance in fat. It is not necessary to wait until the maximal dose of... 

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