New quinoxaline derivatives as potential MT₁ and MT₂ receptor ligands.

Ever since the idea arose that melatonin might promote sleep and resynchronize circadian rhythms, many research groups have centered their efforts on obtaining new melatonin receptor ligands whose pharmacophores include an aliphatic chain of variable length united to an N-alkylamide and a methoxy group (or a bioisostere), linked to a central ring. Substitution of the indole ring found in melatonin with a naphthalene or quinoline ring leads to compounds of similar affinity. The next step in this structural approximation is to introduce a quinoxaline ring (a bioisostere of the quinoline and naphthalene rings) as the central nucleus of future melatoninergic ligand

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

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

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

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