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 ligands. We focused on a difference in structural flexibility between haloperidol and apomorphine, and studied chemical modification of apomorphine, a compound with high affinity for dopamine D2 receptors but not for sigma 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 D2 receptors. Furthermore, carbazole analogues, compounds designed from 6H-dibenzo[b,d]pyran analogues, potentially acted at sigma receptors with high selectivity. This paper describes the design, synthesis and sigma/D2 selectivity of 6H-dibenzo[b,d]pyran and carbazole analogues.
Nakazato
A
A
1st Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, Japan. s10968@ccm.taisho.co.jp
Sekiguchi
Y
Y
Ohta
K
K
Chaki
S
S
Okuyama
S
S
D000818:Animals; D001058:Apomorphine / Q000737:chemistry / Q000378:metabolism*; D001578:Benzopyrans / Q000737:chemistry* / Q000378:metabolism; D002227:Carbazoles / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000378:metabolism*; D013057:Spectrum Analysis
D001578:Benzopyrans; D002227:Carbazoles; D017480:Receptors, sigma; D001058:Apomorphine