Dopamine receptor ligands. Part 18: (1) modification of the structural skeleton of indolobenzazecine-type dopamine receptor antagonists.
On the basis of the D(1/5)-selective dopamine antagonist LE 300 (1), an indolo[3,2-f]benzazecine derivative, we changed the annulation pattern of the heterocycles. The target compounds represent novel heterocyclic ring systems. The most constrained indolo[4,3a,3-ef]benzazecine 2 was inactive, but the indolo[4,3a,3-fg]benzazacycloundecene 3 showed antagonistic properties (functional Ca(2+) assay) with nanomolar affinities (radioligand binding) for all dopamine receptor subtypes, whereas the indolo[2,3-f]benzazecine 4 displayed a selectivity profile similar to 3 but with decreased affinities.
Robaa
Dina
D
Institut für Pharmazie, Lehrstuhl fur Pharmazeutische/Medizinische Chemie, Friedrich-Schiller-Universität Jena, Philosophenweg 14, D-07743 Jena, Germany.
Enzensperger
Christoph
C
Abul Azm
Shams El Din
Sel D
El Khawass
El Sayeda
el S
El Sayed
Ola
O
Lehmann
Jochen
J
D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D018492:Dopamine Antagonists / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D015394:Molecular Structure; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D050641:Receptors, Dopamine D5 / Q000037:antagonists & inhibitors / Q000378:metabolism
C409874:7-methyl-6,7,8,9,14,15-hexahydro-5H-benz(d)indolo(2,3-g)azecine; D018492:Dopamine Antagonists; D007211:Indoles; D008024:Ligands; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D050641:Receptors, Dopamine D5