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 ch ains on the nitrogen atom of the benzoxazine or benzothiazine ring were inv estigated 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 activi ty was studied in right atria of guinea pigs. The benzoxazine derivative wi th 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. Ben zoxazine derivatives with a methylpiperazinylcarbonyl (MS 64) or a N-dimeth ylaminoethylcarboxamide side chain (MS 66) and the benzothiazine derivative (MS 65) with an analog side chain like MS 66 only had a weak effect. We co nclude that the oxygen atom in the heterocyclic ring and the lipophilic sid e chain on the nitrogen atom, which is almost identical with the calcium an tagonistic drug KT-362 is responsible for the most potent action.