title: 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.
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 (7 and 8) 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 11 with alkylamines. 9-(Alkylamino)-4-methylthieno[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. Most of the title compounds 3-6 were found to have neuroleptic activity. In addition, introduction of a 3-chloro substituent in the oxygen and sulfur systems (3p and 4c), as well as introduction of an N-alkyl in the dinitrogen system (6), was found to produce antidepressant effects. Structure-activity relationships are discussed.
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis; D014150:Antipsychotic Agents / Q000138:chemical synthesis; D001381:Azepines / Q000138:chemical synthesis*; D001569:Benzodiazepines / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D007769:Lactams; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010077:Oxazepines / Q000138:chemical synthesis*; D011619:Psychotropic Drugs / Q000138:chemical synthesis*; D051381:Rats; D013329:Structure-Activity Relationship; D013841:Thiazepines / Q000138:chemical synthesis*; D013876:Thiophenes / Q000138:chemical synthesis*
chemical_list: D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D001381:Azepines; D007769:Lactams; D010077:Oxazepines; D011619:Psychotropic Drugs; D013841:Thiazepines; D013876:Thiophenes; D001569:Benzodiazepines