RESUMO
An efficient synthetic approach leading to introduction of the hydroxymethyl group to an aryl moiety via combination of the Bouveault formylation and hydride reduction has been optimized using a rational, mechanistic-based approach. This approach enabled telescoping of the two steps into a single efficient process, readily amenable to scaleup.
Assuntos
Aldeídos/síntese química , Morfolinas/síntese química , Álcool Feniletílico/síntese química , Antidepressivos/química , Humanos , Estrutura Molecular , Morfolinas/química , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/química , EstereoisomerismoRESUMO
We report the novel combination of a selective beta adrenoceptor modulator and a norepinephrine-serotonin uptake inhibitor (sibutramine) with potential for the treatment of obesity. The synthesis and characterization of 6-[4-[2-[[(2S)-3-(9H-carbazol-4-yloxy)-2-hydroxypropyl]amino]-2-methylpropyl]phenoxy]pyridine-3-carboxamide (LY377604), a human ß3-adrenergic receptor agonist and ß1- and ß2-adrenergic receptor antagonist with no sympathomimetic activity at the ß1- and ß2-adrenergic receptors, is reported. Some in vivo data in both rats and humans is presented.