7-Methyl-6,7,8,9,14,15-hexahydro-5H-benz[d]indolo[2,3-g]azecine: a new heterocyclic system and a new lead compound for dopamine receptor antagonists.
Partially hydrogenated derivatives of the new heterocyclic ring systems benz[d]indolo[2,3-g]azecine and bisindolo[3,2-d][2, 3-g]azecine were synthesized starting from lactones and amines via the described synthetic methods. In binding assays with rat striatal receptors, 7-methyl-6,7,8,9,14,15-hexahydro-5H-benz[d]indolo[2, 3-g]azecine (LE 300) proved to be of high affinity for the D(1) binding site (K(i) = 0.08 nmol for displacement of [(3)H]SCH23390), being superior in this assay to standards such as butaclamol and SCH23390. This compound was characterized as a dopamine antagonist by conditioned avoidance response test with mice. Thus, LE 300 represents the lead of a new class of dopamine antagonists for future investigations.
Witt
T
T
Institute of Pharmacy, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.
Hock
F J
FJ
Lehmann
J
J
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001552:Benzazepines / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D002069:Butaclamol / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D018492:Dopamine Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008968:Molecular Conformation; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D013552:Swine
C409874:7-methyl-6,7,8,9,14,15-hexahydro-5H-benz(d)indolo(2,3-g)azecine; D001552:Benzazepines; D018492:Dopamine Antagonists; D007211:Indoles; D017447:Receptors, Dopamine D1; D002069:Butaclamol