RESUMO
Fifteen new alpha-acylaminoketones were prepared by four different routes in an initial effort to optimize the potency of these compounds as ecdysone agonists. The compounds were assayed in mammalian cells expressing the ecdysone receptors from Bombyx mori (BmEcR) and Choristoneura fumiferana (CfEcR) for their ability to cause expression of a reporter gene downstream of an ecdysone response element. A new alpha-acylaminoketone was identified which had activity equal to that of the standard dibenzoylhydrazine ecdysone agonist GS()-E in the assay based on CfEcR.
Assuntos
Ecdisona/agonistas , Regulação da Expressão Gênica/efeitos dos fármacos , Cetonas/síntese química , Cetonas/farmacologia , Animais , Bombyx , Células CHO , Cricetinae , Genes Reporter , Cetonas/química , Lepidópteros , Estrutura Molecular , Receptores de Esteroides/biossíntese , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Ativação Transcricional/efeitos dos fármacos , beta-Galactosidase/biossíntese , beta-Galactosidase/genéticaRESUMO
A library of 35 cis-1-benzoyl-2-methyl-4-(phenylamino)-1,2,3,4-tetrahydroquinolines was prepared. The compounds bore various substitutuents on the benzoyl ring, at the 4-position of the phenylamino ring and at the 6-position of the tetrahydroquinoline ring. The compounds were assayed for their ability to cause expression of a reporter gene downstream of an ecdysone response element in a mammalian cell line engineered to express the ecdysone receptor from Aedes aegypti. In general, compounds with small lipophilic substituents at the meta and para-positions of the benzoyl ring and hydrogen or fluorine at the 4-position of the phenylamino ring and the 6-position of the tetrahydroquinoline ring were the most potent.
