Preparation of some 10-[3-(dimethylamino)-1-propyl]-10H-pyrazino[2,3-b][1,4] benzothiazines as potential neuroleptics.
Chloro- and methyl-substituted 10H-pyrazino[2,3-b][1,4]benzothiazines were prepared and their structures determined by 13C NMR and X-ray crystallographic analysis. Alkylation afforded the 10-[3-(dimethylamino)-1-propyl] derivatives, which were compared to chlorpromazine in receptor-binding assays, in vivo behavioral tests, and electrochemical oxidation studies. In this series, the 2-chloro compound, 4c, proved to be the most effective derivative in displacing [3H]siperone, [3H]apomorphine, and [3H]prazosin radioligands from binding sites, being approximately as potent as chlorpromazine in this respect. However, none of the 10H-pyrazino[2,3-b][1,4]benzothiazines of this study were as active as chlorpromazine in in vivo tests predictive of neuroleptic activity.
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis*; D001667:Binding, Competitive; D002421:Caudate Nucleus / Q000378:metabolism; D003461:Crystallography; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011187:Posture; D011719:Pyrazines / Q000138:chemical synthesis*; D011954:Receptors, Dopamine / Q000378:metabolism; D014965:X-Rays
D014150:Antipsychotic Agents; D011719:Pyrazines; D011954:Receptors, Dopamine