Thiophene systems. 5. Thieno[3,4-b][1,5]benzoxazepines, thieno[3,4-b][1,5]benzothiazepines, and thieno[3,4-b][1,4]benzodiazepines as potential central nervous system agents

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Abstract
10-(Alkylamino)thieno[3,4-b][1,5]benzoxazepines (3) and 10-(alkylamino)thieno[3,4-b][1,5]benzothiazepines (4) were prepared by derivatization of the respective lactams via phosphorus pentachloride and subsequent condensation with the appropriate alkylamines. 9-(Alkylamino)-4H-thieno[3,4-b][1,4]benzodiazepines (5) were prepared by titanium tetrachloride catalyzed condensation of the lactam with alkylamines. 9-(Alkylamino)-4-methyl-thieno[3,4-b][1,4]benzodiazepines (6) were prepared by reductive alkylation of 5. The compounds were tested for potential neuroleptic activity by means of the blockade of d-amphetamine lethality in aggregated mice and/or effects on locomotor activity in rats. Antidepressant activity was examined using inhibition of tetrabenazine-induced depression in mice. The compounds 3-6 had neuroleptic activity. Introduction of a 3-chloro substituent in the O and S systems (3p and 4c), and introduction of an N-alkyl in the N2 system (6) produced antidepressent effects. Structure-activity relationships are discussed.