Abstract
The coronary vasodilating action of 1, 5-benzothiazepine derivatives and the structureactivity relationship were examined in the anesthetized dog. 2-(4-Methoxyphenyl), 3-acyloxy or alkyloxy, 5-dimethylaminoethyl and 7-hydrogen moieties were important for vasodilation. The action of the derivatives was found to be stereospecific for the d-cis-isomer. Based on these findings, it can be concluded that d-3-acetoxy-cis-2, 3-dihydro-5-[2-(dimethylamino) ethyl]-2-(4-methoxyphenyl)-1, 5-benzothiazepin-4 (5H)-one hydrochloride (CRD-401) was the most potent compound among the derivatives tested. The metabolites of dl-isomer of CRD-401, i.e. deacetyl and deacetyl-O-or N-demethyl compounds, were less active and less toxic than the parent compound.
