C. Studenik et al., New benzoxazine and benzothiazine derivatives - structure-activity relations in guinea-pig heart and smooth muscle preparations, PHARMAZIE, 54(5), 1999, pp. 330-334
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.