Synthesis and dopamine receptor binding studies of homochiral 8-aminopyrido[1,2-a]indoles.
Starting from L-aspartic acid the preparation of 8-aminopyrido[1,2-a]indole derivatives as benzo-fused analogs of the dopamine autoreceptor agonist 1 is reported. The key step of the synthesis is the Tf2O induced cyclization of the 1,2-amino alcohol 6. Receptor binding studies indicated selective affinity for the D-2 autoreceptor. Among the tested compounds, the dipropylamino derivative 2 showed the highest affinity for the D-2 receptor labelled with the selective autoreceptor agonist pramipexole (IC50 value: 450 nM). Thus, 2 is 15 times less potent than the aminoindolizine 1.
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017660:Autoreceptors / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D052160:Benzothiazoles; D018491:Dopamine Agonists / Q000737:chemistry* / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D000077487:Pramipexole; D011954:Receptors, Dopamine / Q000187:drug effects*; D013134:Spiperone / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D017660:Autoreceptors; D001552:Benzazepines; D052160:Benzothiazoles; D018491:Dopamine Agonists; D007211:Indoles; D011954:Receptors, Dopamine; D013844:Thiazoles; D001224:Aspartic Acid; D013134:Spiperone; D000077487:Pramipexole