New benzoxazine and benzothiazine derivatives--structure-activity relations in guinea-pig heart and smooth muscle preparations.
New benzoxazine and benzothiazine derivatives which differ in their side chains on the nitrogen atom of the benzoxazine or benzothiazine ring were investigated regarding structure-activity relations and compared with calcium antagonistic drugs. The isometric contraction force was measured in guinea-pig papillary muscles, aortic strips and terminal ilea. Chronotropic activity was studied in right atria of guinea pigs. The benzoxazine derivative with a dimethoxyphenylethyl-N-methylaminoethylcarboxamide side chain (MS 84) had the most potent negative inotropic effect on papillary muscles and the most potent relaxing effect on terminal ilea. The benzothiazine derivative with a methylpiperazinylcarbonyl side chain (MS 63) was less effective. Benzoxazine derivatives with a methylpiperazinylcarbonyl (MS 64) or a N-dimethylaminoethylcarboxamide side chain (MS 66) and the benzothiazine derivative (MS 65) with an analog side chain like MS 66 only had a weak effect. We conclude that the oxygen atom in the heterocyclic ring and the lipophilic side chain on the nitrogen atom, which is almost identical with the calcium antagonistic drug KT-362 is responsible for the most potent action.
Studenik
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C
Institute of Pharmacology and Toxicology, University of Vienna, Austria. Christian.Studenik@univie.ac.at
Lemmens-Gruber
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R
Heistracher
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D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010078:Oxazines / Q000138:chemical synthesis* / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis* / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010078:Oxazines; D013843:Thiazines