cis-1,2,3a,4,5,9b-hexahydro-3H-benz[e]indoles: synthesis and in vitro binding affinity at dopamine D1 and D2 receptors.
cis-1,2,3a,4,5,9b-Hexahydro-3H-benz[e]indoles were synthesized and evaluated for in vitro dopamine D1 and D2 receptor binding affinity. The target compounds 21-25 were readily prepared by reduction of the air-sensitive tricyclic enamines 10-14. Reduction of 10-14 with sodium borohydride, sodium cyanoborohydride, palladium on carbon in ethanol, and platinum oxide in ethanol or acetic acid gave only the cis (3a,9b) 1,2,3a,4,5,9b-hexahydro-3H-benz[e]indoles. The stereochemistry was confirmed by single-crystal X-ray analysis. In the 6-hydroxy series, the binding affinity at D1 and D2 receptors was of the order 22 (N-n-butyl) > 21 (N-n-propyl) > 23 (N-H). The compounds demonstrated greater binding affinity at D2 receptors than at D1 binding sites. In contrast, 8-OH derivatives exhibited affinity only for D2 receptors, with 25 (N-n-butyl) having slightly greater affinity than 24 (N-n-propyl).
Cruse
S F
SF
School of Pharmacy, Northeast Louisiana University, Monroe 71209-0470.
Lear
J
J
Klein
C L
CL
Andersen
P H
PH
Dick
R M
RM
Crider
A M
AM
D000818:Animals; D001552:Benzazepines / Q000378:metabolism / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014316:Tritium
D001552:Benzazepines; D015259:Dopamine Agents; D007211:Indoles; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014316:Tritium; D013134:Spiperone