RESUMEN
Despite the high prevalence of neuropsychiatric disorders, their aetiology and molecular mechanisms remain poorly understood. The zebrafish (Danio rerio) is increasingly utilized as a powerful animal model in neuropharmacology research and in vivo drug screening. Collectively, this makes zebrafish a useful tool for drug discovery and the identification of disordered molecular pathways. Here, we discuss zebrafish models of selected human neuropsychiatric disorders and drug-induced phenotypes. As well as covering a broad range of brain disorders (from anxiety and psychoses to neurodegeneration), we also summarize recent developments in zebrafish genetics and small molecule screening, which markedly enhance the disease modelling and the discovery of novel drug targets.
Asunto(s)
Fármacos del Sistema Nervioso Central/uso terapéutico , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Modelos Animales de Enfermedad , Descubrimiento de Drogas , Bibliotecas de Moléculas Pequeñas/uso terapéutico , Animales , Fármacos del Sistema Nervioso Central/síntesis química , Fármacos del Sistema Nervioso Central/química , Evaluación Preclínica de Medicamentos , Bibliotecas de Moléculas Pequeñas/síntesis química , Bibliotecas de Moléculas Pequeñas/química , Pez CebraRESUMEN
The title compound, C 11H12N4O2,was prepared via the transformation of sodium 4-acetyl-1-phenyl-1H-[1.2.3]triazolate under the action of meth-oxy-amine hydro-chloride. The dihedral angle between the triazole and phenyl rings is 25.12â (16)° and the C atom of the meth-oxy group deviates from the triazole plane by 0.894â (4)Å. The conformation of the CONHR-group is consolodated by an intra-molecular N-Hâ¯N hydrogen bond to an N-atom of the triazole ring, which closes an S(5) ring. In the crystal, weak N-Hâ¯N hydrogen bonds link the mol-ecules into C(6) [010] chains.
RESUMEN
The tert-amino reaction effect was examined. A new method to synthesize spiro heterocycles is presented. It was shown that the "tert-amino effect" could be applied to the formation of spiro-fused heterocycles. The formation of spiro compounds proceeds in most cases in good yields in a one-pot reaction.
Asunto(s)
Compuestos Heterocíclicos/química , Compuestos de Espiro/síntesis química , Espectroscopía de Resonancia Magnética , Protones , Compuestos de Espiro/químicaRESUMEN
A systematic study of the reactions of dimethyl acetylenedicarboxylate (DMAD) and methyl propynoate with 5-mercaptoazoles and pyridine-2-thiones has been carried out and as a result, a number of novel imidazo[1,5-b]thiazin-4-ones 6a,b, pyrazolo[1,5-b] thiazin-4-ones 15a-f, imidazo[1,5-b]thiazol-4-ones 7a,b and thiazolo[3,2-a]pyridines 21a-c have been prepared. The influence of the size of the ring of the starting "cyclic" thioamides on the size of the fused ring in the reaction products has been established. The preferred formation of a six-membered thiazine ring took place in the reactions of 5-mercaptoazoles. In contrast, the five membered thiazolidine ring is formed in reactions of pyridine-2-thiones. In both cases the product is a five-membered ring fused to a six-membered heterocycle.