Background: The benzoxazepine JL13 is an analogue of the clozapine family of antipsychotic
agents which target the 5-HT2A receptor, and has showed promise as an atypical antipsychotic
agent. Based on the dearth of clinically effective anti-psychotic agents available, we sought to
design and chemically synthesize additional analogues.
Methods: Structure function analysis was conducted using state of art computational methods, which
were designed to highlight new candidates for chemical synthesis. Efficient syntheses were then conducted
and the products screened for affinity to the receptor.
Results: Among many new analogues prepared, an aza analogue demonstrated seventeen times greater
affinity for the receptor than JL13.
Conclusion: An efficient synthetic route to an aza-analogue of JL13 was developed and will allow
rapid modifications of the core and synthesis of related libraries.