Autism spectrum disorder is a neurodevelopmental disease with increasing occurrence. Recent studies focus on the development of novel V1A receptor antagonists which can influence the core symptoms of autism through the AVP pathway. In this study, we describe the synthesis of new heterocyclic ring systems. These are a novel class of brain-penetrating V1A antagonists with improved metabolic stability and in vivo potency. The efficacy of the compounds was strongly influenced by the position of the chlorine atom, suggesting halogen bond formation between the ligands and the V1A receptor.
Keywords: ASD; CNS; V1A receptor; halogen bonding; imidazo[1,2-a][1,2,4]triazolo[4,3-c][1,3]diazepine; imidazo[1,2-a][1,2,4]triazolo[4,3-c][1,3]diazocine.