RESUMO
The discovery of a series of 4-aminoethyl-3-(phenylsulfonyl)-1H-indoles, dual acting norepinephrine reuptake inhibitors (NRIs) and 5-HT(2A) receptor antagonists, is described. The synthesis and structure-activity relationship (SAR) of this novel series of compounds is also presented.
Assuntos
Indóis/farmacologia , Inibidores da Captação de Neurotransmissores/síntese química , Inibidores da Captação de Neurotransmissores/farmacologia , Norepinefrina/metabolismo , Antagonistas do Receptor 5-HT2 de Serotonina , Antagonistas da Serotonina/síntese química , Antagonistas da Serotonina/farmacologia , Transporte Biológico/efeitos dos fármacos , Linhagem Celular , Humanos , Indóis/síntese química , Indóis/metabolismo , Inibidores da Captação de Neurotransmissores/metabolismo , Receptor 5-HT2A de Serotonina/metabolismo , Antagonistas da Serotonina/metabolismo , Relação Estrutura-AtividadeRESUMO
The SAR of a series of 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ols as monoamine reuptake inhibitors, with a goal to improve both potency toward inhibiting the norepinephrine transporter and selectivity over the serotonin transporter, is reported. The effect of specific substitution on both the 3-phenyl group and the indole moiety were explored. This study led to the discovery of compound 20 which inhibited the norepinephrine transporter with an IC50 value of 4 nM while exhibiting 86-fold selectivity over the serotonin transporter.