Studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines. II. Synthesis of new series of 1- or 2-substituted 4H-s-triazolo[3,4-c]-1,4-benzothiazines and related compounds with potential CNS activity.
New series of 1- or 2-substituted 4H-s-triazolo[3,4-c]-1,4-benzothiazines have been prepared. The 1-substituted products were obtained starting from 3-hydrazino-2H-1,4-benzothiazine derivatives (III) by treatment with chloroacethyl chloride followed by cyclization of the resulting chloroacethylderivatives into the chloromethyltriazolobenzothiazines (IV a-e), which were then reacted with the appropriate amines to give the desired compounds (V a-n). Other 1-substituted compounds were prepared by ring closure of (III) with cyanogen bromide, affording 1-amino-4H-s-triazolo [3,4-c]-1,4-benzothiazines (XI a-e). The 2-substituted compounds (VIII) were prepared from 2,4-dihydro-1H-s-triazolo [3,4-c]-1,4-benzothiazin-1-ones (VII), synthesized from (I) by reaction with ethyl carbazate. The aminoalkyl side chain was introduced into (VII) in two steps: first by treatment with 1-bromo-3-chloropropane, then by refluxing the resulting product with the appropriate amine. Some 4H-tetrazolo[5,1-c]-1,4-benzothiazines (XII) were also synthesized from (III). Preliminary pharmacological data on the CNS activity of the synthesized tricyclic compounds are reported.
Grandolini
G
G
Istituto di Chimica Farmaceutica e Tecnica Farmaceutica, Università di Perugia, Italy.
Tiralti
M C
MC
Rossi
C
C
Ambrogi
V
V
Orzalesi
G
G
De Regis
M
M
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis; D002491:Central Nervous System Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D013055:Spectrophotometry, Infrared; D013843:Thiazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
D000927:Anticonvulsants; D002491:Central Nervous System Agents; D013843:Thiazines; D014230:Triazoles