RESUMO
A practicable six-step synthetic pathway has been developed to access a library of novel 3-[(N-cycloalkylbenzamido)methyl]-2-quinolones using Morita-Baylis-Hillman methodology. These compounds and their 3-[(N-cycloalkylamino)methyl]-2-quinolone precursors have been screened as potential HIV-1 integrase (IN) inhibitors. A concomitant survey of their activity against HIV-1 protease and reverse-transcriptase reveals selective inhibition of HIV-1 IN.
Assuntos
Inibidores de Integrase de HIV/síntese química , Integrase de HIV/química , HIV-1/enzimologia , Quinolonas/química , Sobrevivência Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Células HEK293 , Integrase de HIV/metabolismo , Inibidores de Integrase de HIV/metabolismo , Inibidores de Integrase de HIV/farmacologia , Transcriptase Reversa do HIV/antagonistas & inibidores , Transcriptase Reversa do HIV/metabolismo , Humanos , Quinolonas/metabolismo , Quinolonas/farmacologia , Relação Estrutura-AtividadeRESUMO
An efficient reaction protocol was developed for the synthesis of several diindolylmethane derivatives via the [Formula: see text] C-H bond activation of aryl methyl ketones by [Formula: see text] and indoles in the presence of catalytic amounts of [Formula: see text] at 80 [Formula: see text] using dioxane as solvent. Unexpectedly, an interesting class of di(3-indolyl)selenide compounds was isolated when the reaction was carried out at room temperature.
Assuntos
Indóis/síntese química , Iodetos/química , Óxidos de Selênio/síntese química , Catálise , Cristalografia por Raios X , Ligação de Hidrogênio , Indóis/química , Iodo/química , Modelos Moleculares , Estrutura Molecular , Óxidos de Selênio/químicaRESUMO
Novel 3-hydroxy-3-phenylpropanoate ester-azidothymidine (AZT) conjugates have been prepared using Baylis-Hillman methodology, and their potential as dual-action HIV-1 Integrase and Reverse Transcriptase inhibitors has been explored using enzyme inhibition and computer modelling techniques; their activity and HeLa cell toxicity have been compared with those of their cinnamate ester analogues.
Assuntos
Inibidores de Integrase de HIV/química , Inibidores de Integrase de HIV/farmacologia , HIV-1/efeitos dos fármacos , Inibidores da Transcriptase Reversa/química , Inibidores da Transcriptase Reversa/farmacologia , Zidovudina/química , Zidovudina/farmacologia , Fármacos Anti-HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Integrase de HIV/metabolismo , Inibidores de Integrase de HIV/síntese química , Transcriptase Reversa do HIV/antagonistas & inibidores , Transcriptase Reversa do HIV/metabolismo , HIV-1/enzimologia , Células HeLa , Humanos , Simulação de Acoplamento Molecular , Inibidores da Transcriptase Reversa/síntese química , Relação Estrutura-Atividade , Zidovudina/síntese químicaRESUMO
One-pot multi-component reaction of 3-cyanoacetyl indole, aromatic aldehydes and ethyl acetoacetate in the presence of InCl(3)/NH(4)OAc under microwave irradiation for 2-7 min afforded novel and highly functionalized 3-(pyranyl)- and 3-(dihydropyridinyl)indole derivatives, respectively, in good yield.
Assuntos
Técnicas de Química Sintética , Indóis/síntese química , Micro-Ondas , Indóis/químicaRESUMO
In this study, we report the synthesis of several novel dihydroisoxazole-, tetrahydroisoxazole- and dihydropyrazole-fused pyrido[2,3-b]quinolines, α-carbolines, and pyrido[2,3-c]coumarins, respectively, from simple precursors and by exploring intramolecular 1,3-dipolar cycloaddition reactions involving nitrile oxides, nitrones, and nitrile imines as 1,3-dipoles.
