RESUMO
A number of novel imidazophenoxazine-4-sulfonamides have been designed as potential inhibitors of PDE4. All these compounds were readily prepared via an elegant multi-step method involving the initial construction of 1-nitro-10H-phenoxazine ring and then fused imidazole ring as key steps. Some of these compounds showed promising PDE4B and D inhibition when tested in vitro and good interactions with these proteins in silico. Three of these compounds showed dose dependent inhibition of PDE4B with IC50 value of 3.31 ± 0.62, 1.23 ± 0.18 and 0.53 ± 0.18 µM.
Assuntos
Oxazinas/química , Oxazinas/farmacologia , Inibidores da Fosfodiesterase 4/química , Inibidores da Fosfodiesterase 4/farmacologia , Sulfonamidas/química , Sulfonamidas/farmacologia , Animais , Linhagem Celular , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Simulação de Acoplamento Molecular , Oxazinas/síntese química , Sulfonamidas/síntese químicaRESUMO
A rapid, versatile and one-pot Cu-mediated domino reaction has been developed for facile assembly of two six membered fused N-heterocyclic rings leading to novel small molecules as potential inhibitors of PDE4.
RESUMO
A number of novel 1,8-disubstituted 5,5-dimethyl-4,5-dihydro-1H-benzo[g]indazoles based on a conformationally restricted pyrazole framework have been designed as potential inhibitors of PDE4. All these compounds were readily prepared by using simple chemistry strategy. The in vitro PDE4B inhibitory properties and molecular modeling studies of some of the compounds synthesized along with the X-ray single crystal data of a representative compound is presented.