The tertiary amine nitrogen atom of piperazine sulfonamides as a novel determinant of potent and selective beta3-adrenoceptor agonists.

Novel compounds were prepared in fair to good yields as human beta(3)-adrenoceptor (beta(3)-AR) agonists. In particular, aryloxypropanolamines 7 a-d (EC(50)=0.57-2.

Stereospecific synthesis and bio-activity of novel beta(3)-adrenoceptor agonists and inverse agonists.

Since it is widely distributed into the body, beta(3)-adrenoceptor is becoming an attractive target for the treatment of several pathologies such as obesity, type 2 diabetes, metabolic syndrome, cachexia, overactive bladder, ulcero-inflammatory disorder of the gut, preterm labour, anxiety and depressive disorders, and heart failure. New compounds belonging to the class of arylethanolamines bearing one or two stereogenic centres were prepared in good yields as racemates and optically active forms. They were, then, evaluated for their intrinsic activity towards beta(3)-adrenoceptor and their affinity for beta(1)- and beta(2)-adrenergic receptors.

A chemoenzymatic scalable route to optically active (R)-1-(pyridin-3-yl)-2-aminoethanol, valuable moiety of beta3-adrenergic receptor agonists.

Enantiomerically pure (R)-2-chloro-1-(pyridin-3-yl)ethanol has been prepared by kinetic resolution performed in the presence of Candida antarctica SP435-L lipase immobilized on a macroporous polyacrylate resin (Novozym 435). It was converted into (R)-1-(pyridin-3-yl)-2-aminoethanol, left-hand side of beta(3)-adrenergic receptor ligands.

Synthesis and biological evaluation of new clofibrate analogues as potential PPARalpha agonists.

Clofibrate is a lipid-profile modifying agent belonging to the fibrate class of drugs. Fibrates are known to exhibit their beneficial effects by activating peroxisome proliferator-activated receptor-alpha (PPARalpha) and used in the treatment of dyslipidemia and atherosclerosis and for the prevention of heart failure. Hereby, the preparation of two new sets of clofibrate analogues, ethyl 2-(4-chlorophenoxy)-3-oxoalkanoates and ethyl 2-(4-chlorophenoxy)-3-hydroxyalkanoates is described starting from commercially available 3-oxoalkanoates in fair to good yields.