Chemical modification of apomorphine to discover sigma ligands: 6H-dibenzo[b,d]pyran and carbazole analogues

It seems that many sigma ligands have been designed from known sigma ligand s. We focused on a difference in structural flexibility between haloperidol and apomorphine, and studied chemical modification of apomorphine, a compo und with high affinity for dopamine D-2 receptors but not for a receptors, for discovery of sigma ligands. The first modification yielded good results with 6H-dibenzo[b,d]pyran analogues with weak affinity for sigma receptors but not D-2 receptors. Furthermore, carbazole analogues, compounds designe d from 6H-dibenzo[b,d]pyran analogues, potentially acted at sigma receptors with high selectivity. This paper describes the design, synthesis and sigm a/D-2 selectivity of 6H-dibenzo[b,d]pyran and carbazole analogues. (C) 1999 Elsevier Science Ltd. All rights reserved.