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.
Various (±)-trans-2-arylnitrocyclohexane derivatives were hydrogenated to the corresponding amines over a Pd/C catalyst in methanol at 25-60°C and 1-12 bar. These (±)-trans-2-arylcyclohexylamines are important and valuable key intermediates for the stereoselective synthesis of phenantridine-based Amaryllidaceae alkaloid analogues having cytostatic activity.
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