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Type 2 diabetes is responsible for various micro and macro-vascular complications, appearing early in the course of the disease. The UKPDS results clearly demonstrate the interest of an early and intensive treatment of hyperglycaemia to reduce theses microvascular complications and, to a lesser extent, macrovascular complications. The UKPDS also demonstrate the limits of the current management of type 2 diabetes: delayed diagnosis when several complications already exist, difficulties to maintain an adequate glucose control over the time, particularly with monotherapy, need for an intensive combination treatment policy, unwanted effects of this intensive treatment (weight gain, hypoglycaemias). The 3 classes of oral antidiabetic agents currently available (sulfonylureas and meteglinide analogues, metformin, a-glucosidase inhibitors) imperfectly cover the current therapeutic needs. Thus, the new class, the thiazolidinediones, acting on key physiopathological components, appears as a welcome addition to the treatment of type 2 diabetes. The association of metformin (or a sulfonylurea) and a thiazolidinedione should permit to obtain early a better glycaemic control without the hypoglycaemic risk associated with intensive therapy at an early stage of type 2 diabetes.

The European marketing authorization ( product licence ) for thiazolidinediones (rosiglitazone and pioglitazone) contraindicate their use in type 2 diabetic patients with cardiac failure or history of cardiac failure. A warning and special precautions for use apply to fluid retention and cardiac failure. The main experimental and clinical data currently available are reviewed. Guidance are given to prescribing physician for the initiation of thiazolidinediones in type 2 diabetic patients and for management of these patients, particularly those at risk for cardiac failure. The cardiologist advice (and possibly diagnosis by echocardiography) is recommended when clinical doubts exist.

We studied a new family of aldose-reductase inhibitors with an imidazolidine arylmethylene and thiazolidine-acetate structure susceptible to prevent ocular, renal and vascular complications of insulin-dependent diabetes mellitus. We examined the role of the enzyme in the pathological processes involved and reviewed knowledge of known aldose reductase inhibitors leading to the development of the basic structure modulated to have insight into the different elements of the structure-quantitative activity relationship. Potential inhibitors are synthesized by condensation of heterocyclic rings and aldehyde aromatic rings. Their identity and structure were established by magnetic resonance spectroscopy (MRS) based on proton-carbon couplage constants and the homonuclear NOE effect. The structure-activity correlations were analyzed on the basis of the IC50 using a structural model and a physicAL model which showed the importance of the sulfur atom in the heterocyclic ring due to its important lipophilic contribution. Finally, a molecular modeling approach led to a provisional descriptive model of the inhibitor-enzyme interaction.

The synthesis and physico-chemical properties of fourteen 4-thio-5-arylidene-thiazolidine-2-ones and eight 3-(4-bromophenacyl)-4-thio-5-arylidene-thiazolidine-2-ones are described. These products were synthetized by the aldolisation-crotonisation reaction between aromatic aldehydes and 4-thio-thiazolidine-2-one followed by N-alkylation of this substituted compounds.

Synthesis and physico-chemical properties of four 3-benzyl or 3-(4-chlorobenzyl)-4-thioxo-5-arylazo-imidazolidin-2-ones, five 3-(4-nitrobenzyl)-5-arylidenethiazolidine-2,4-diones and three 3-(4-phenyl-phenacyl)-4-thioxo-5-arylidenethiazolidin-2-ones have been described. These new products were synthesized by an aldolisation-crotonisation reaction from aromatic aldehydes and 3-substituted thioxothiazolidin-2-ones or thiazolidine-2,4-diones. The arylazo-imidazolidine compounds were synthesized by copulation of diazonium ions with imidazolidines. Antimicrobial activity was determined for some compounds.

The synthesis and the physico-chemical properties of four 3-(4-bromophenacyl)-5-arylidene-thiazolidine-2,4-diones, two 3-(4-bromobenzyl)-5-arylidene-thiazolidine-2,4-diones and seven 3-(4-chlorobenzyl)-5-arylidene-4-thio-imidazolidine-2-ones were described. These products were synthetized by the aldolisation-crotonisation reaction between aromatic aldehydes and substituted thiazolidinediones or thio-imidazolidinones.