Diseño, síntesis y evaluación biológica de nuevos antagonistas del receptor y5 del neuropeptido y como potenciales agentes terapéuticos para el tratamiento de la obesidad

Resumen

Diseño, síntesis y evaluación biológica de nuevos antagonistas del receptor Y5 del neuropeptido y como potenciales agentes terapéuticos para el tratamiento de la obesidad #resumen: Obesity is a worldwide epidemic. its rising prevalence throughout the worid, together with its increased associated morbidity, has become a real healthchallenge in this century and therefore, the treatment of obesity is now of great importance. Obesity is a disease of multi factor etiology due to imbalance between energy intake and energy expenditure. The lack efficacy of the available obesity drugs makes obesity one of the most attractive of therapeutic targets. Many neurotransmitters are involved in this control of feeding behavior. Neuropeptide Y (NPY) has been shown to play an important role in the regulation of food intake and energy balance. The aim of this study is the synthesis and biological evaluation of a series of novel hydrazide, carbohydrazide and piperazine derivatives, structurally related to the sulfonamidomethylcyclohexyl and the sulfonamidomethylpnenyl moieties, as potent and selective human NPY Y5 receptor antagonists for the treatment of obesity. 70 new compounds have been synthetized and have been evaluated for in vitro and in vivo antiobesity activity. The SAR of these series was examined and the carbohydrazide derivatives were the compounds that showed the best activities reaching nanomolar binding affinity to the hY5 receptor. The sulfonamide group and the cyclohexyl linker were found to be essential in the concession or biological activity. In conclusion, optimization of this leader compounds led to the obtainment of new potent antiobesity agents