Diseño, síntesis y evaluación biológica preliminar de nuevos derivados de benzo (b) tiofeno, en la búsqueda de agentes para una nueva terapia antidepresiva

Resumen

Diseño, síntesis y evaluación biológica preliminar de nuevos derivados de Benzo (B) tiofeno, en la búsqueda de agentes para una nueva terapia antidepresiva. Depression is a disease which, according to thw world health organization (who), affects more than 121 million persons throughout the world. In addition, this disease causes a large number of suicidal deaths each year. According to the monoamininergic hypothesis, depression is provocked b y a functional shortage of monoamininergic neurotransmitters, including serotonin (5-HT). Al present, the most frequently used drugs for the treatment of depression are the 5-HT reuptake inhibitors; by means of blocking the 5 HT transporter, these inhibitors provoke an increase in the extracelullular levels of this neurotransmitter, and therefore, the serotoninergic transmission is increased. In this study, the synthesis of dual compounds which inhibit 5- HT reuptake and antagonize the 5- HT7 (5-HT7R) serotoninergic receptors is proposed. These products are used because numerous studies indicate that the 5- HT7R antagonism can provoke antidepressive effects. It has been scientifically proven that 5- HT reuptake inhibition is one of the most effective ways to increase serotoninergic transmission and therefore, results in improved treatment for depression. Diverse arylsulfonamides and arylsulfonamines derived from benzo (b) thiophene have been synthetized. Some of these arylamines have shown great ability in blocking the 5-HT transporter, as well as a complementary antagonic effect on 5-HT7R, making them potential antidpressive agents. The synthetized structures are novel and open a new and important line of research in the search for new compounds with antidepressive activity. From a synthetic point of view, synthetic routes have been optimized and the mechanism of reaction of the reactions carried out have been studied. This study also specifies the structural elucidation of various structures with advanced techniques of nuclear magnetic resonance (HMBC, HMQC, COSY y NOESY).