Diseño, síntesis y evaluación biológica de nuevos derivados de piridazinoindol e indol como agonistas de los receptores MT1/MT2 de melatonina para el tratamiento de los trastornos del sueño
- Autores: Nerea Castrillo Apezteguía
- Directores de la Tesis: Ignacio Aldana Moraza (dir. tes.), Silvia Galiano Ruíz (dir. tes.)
- Lectura: En la Universidad de Navarra ( España ) en 2013
- Idioma: español
- Número de páginas: 373
- Tribunal Calificador de la Tesis: Antonio Monge Vega (presid.), Rosa Maria Tordera (secret.), María Asunción Burguete Pérez (voc.), Fernando Iglesias Guerra (voc.), Marina Gordaliza (voc.)
- Materias:
- Enlaces
- Tesis en acceso abierto en: Dadun
- Resumen
Since melatonin (MLT) was discovered, several physio-pathological functions have been associated with this hormone. One of the most important functions of this natural ligand is the regulation of sleep-wake cycles and its implication in insomnia and other sleep disorders. MLT exerts its actions through two GPCRs receptors, MT1 and MT2, which have been suggested as key targets in this area. Currently, numerous researches have focused their research on new melatoninergic ligands. We have reported design, synthesis and characterization of novel pyridazino[4,5-b]indole (PI) and indole (In) derivatives. In addition, these compounds have been evaluated biologically to melatonin receptors. Based on PI and In biological results, we designed a new pharmacophore to synthesize future leader ligands with potent affinity and activity to melatoninergic receptors with the following characteristics: an indole ring as central core, methoxy group substituted in the 6 position of indole ring, six-atom length distance between methoxy group and the first nitrogen atom of the side chain and two-methylene linker over the indole ring and attached to different nitrogenous chains such as N-acetamide, N-methylurea, N-ethylurea and N-methylsulfonamide.
