Yoshio Imashiro

Biotransformation of Molsidomine (N-Ethoxycarbonyl-3-morpholinosydnonimine), a New Anti-anginal Agent, in Rats

Abstract1. After oral administration of [14C]N-ethoxycarbonyl-3-morpholinosydnon-imine (molsidomine) to rats, 85.0% of the ingested radioactivity was excreted in urine in 24 h. Metabolites found in the urine were molsidomine (0.6% of urinary radioactivity), 3-morpholinosydnonimine (compound A, 8.4%) and N-cyanomethylenaminomorpholine (compound C, 15%). About 48% of urinary radioactivity was accounted for by approximately equal amounts of the two weakly acidic metabolites N-cyanomethylenaminomorpholine-2-one (compound D) and N-cyanomethylenamino-N-(2-hydroxyethyl)-glycine (compound E).2. In 24 h after intraduodenal injection of [14C]molsidomine to rats, 13.3% of the radioactivity was excreted in the gastric juice as molsidomine (95%) and compound C (4.8%). Much of the molsidomine in the gastric juice was present a polar, conjugate-like compound, which on purification by t.l.c. was converted to the parent drug.3. After intravenous injection of [14C]molsidomine to rats, the blood level declined biphasically ...

NEW CEPHALOSPORINS WITH 7-ACYL GROUPS DERIVED FROM β-KETOACIDS

The synthesis and antimicrobial profile of a series of 7-(beta-ketoacylamino)cephalosporins (1) bearing an acetoxymethyl or a heterocyclichiomethyl group at the 3-position are described. Of this series, 3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-7-(3-oxobutyrylamino)ceph-3-em-4-carboxylic acid (11) showed moderate antibacterial activities in in vitro and in vivo tests.