RESUMO
Solid preclinical evidence links vasopressin to social behavior in animals, so, extensive work has been initiated to find new vasopressin V1a receptor antagonists which can improve deteriorated social behavior in humans and can treat the core symptoms of autistic behavior, as well. Our aim was to identify new chemical entities with antagonizing effects on vasopressin V1a receptors. Continuing our previous work, we found an in vitro and in vivo orally active V1a selective antagonist molecule (40) among [1,2,4]triazolo[4,3-a][1]benzazepines.
Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos/síntese química , Benzazepinas/síntese química , Receptores de Vasopressinas/metabolismo , Transtornos do Comportamento Social/tratamento farmacológico , Animais , Antagonistas dos Receptores de Hormônios Antidiuréticos/farmacologia , Benzazepinas/farmacologia , Humanos , Concentração Inibidora 50 , Isomerismo , Camundongos , Microssomos Hepáticos/metabolismo , Ligação Proteica , Quinolonas/química , Ratos , Relação Estrutura-AtividadeRESUMO
Recent advances in the field of continuous flow chemistry allow the multistep preparation of complex molecules such as APIs (Active Pharmaceutical Ingredients) in a telescoped manner. Numerous examples of laboratory-scale applications are described, which are pointing towards novel manufacturing processes of pharmaceutical compounds, in accordance with recent regulatory, economical and quality guidances. The chemical and technical knowledge gained during these studies is considerable; nevertheless, connecting several individual chemical transformations and the attached analytics and purification holds hidden traps. In this review, we summarize innovative solutions for these challenges, in order to benefit chemists aiming to exploit flow chemistry systems for the synthesis of biologically active molecules.
