RESUMO
Alkyl-5,6-diphenylpyridazine derivatives combining several main features of ACAT inhibitors, such as a long alkyl side chain linked to a heterocycle and the o-diphenyl system, were synthesized and tested. Moreover, modeling studies on representative terms were performed. Some compounds displayed ACAT inhibition in the micromolar range, both on the enzyme isolated from rat liver microsomes and in cell-free homogenate of murine macrophages.
Assuntos
Inibidores Enzimáticos/síntese química , Piridazinas/síntese química , Esterol O-Aciltransferase/antagonistas & inibidores , Animais , Sistema Livre de Células , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Técnicas In Vitro , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Camundongos , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Modelos Moleculares , Piridazinas/química , Piridazinas/farmacologia , Ratos , Relação Estrutura-AtividadeRESUMO
QSAR models have been used for designing a series of compounds characterized by a N-phenylpiperazinylalkylamino moiety linked to substituted pyridazinones, which have been synthesized. Measurements of the binding affinities of the new compounds toward the alpha(1a)-, alpha(1b)-, and alpha(1d)-AR cloned subtypes as well as the 5-HT(1A) receptor have been done validating, at least in part, the estimations of the theoretical models. This study provides insight into the structure activity relationships of the alpha(1)-ARs ligands and their alpha(1)-AR/5-HT(1A) selectivity.
