• derivati salicilaldossimici
• derivati tioammidici
• enzima 17beta-HSD1
• Estrogeni
• recettori nucleari

In this thesis, I have synthetized novel compound potentially implicated in the genesis and the development of estrogen-dependent diseases. Most of my work has concerned the synthesis of novel salicylaldoximes in an attempt to obtain estrogen receptor (ER) ligands with improved ER-beta selective affinity and agonist properties. The salicylaldoxime template constitutes a novel class of nonsteroidal ER-ligands that is based on a hydrogen-bonded pseudocyclic ring as a bioisosteric replacement of the phenol ring (functional group present in most estrogen receptor ligands). Among several modifications of previously developed salicylaldoximes, the best results were obtained by the simultaneous exchange of the relative positions of the phenol OH and oxime groups together with the insertion of a chloro group in the 6-position of the central scaffold. The resulting compound showed the best affinity (Ki = 0.38 nM) for ER-beta Another part of my thesis was dedicated to the synthesis of a new compound as a nonsteroidal inhibitor of 17beta-Hydroxysteroid Dehydrogenase Type 1 (17beta-HSD1). This enzyme catalyzes the reduction of estrone (E1) to the highly potent ER-agonist estradiol (E2) and, therefore, it is an important target for the treatment of hormone-dependent diseases, because its inhibition leads to a reduction of the endogenous production of E2.. I have developed a thioamido-derivative able to inhibit the enzyme to a certain extent (20% of inhibition at 1 microM concentration), although other non-steroidal analogues, this level of inhibition turned out to unfavourably compare to previously reported 17beta-HSD1 inhibitors.