Urinary metabolites of 1-(3-Mercapto-2-D-methyl-1-oxopropyl)-L-proline(SQ-14225),a new antihypertensive agent, in rats and dogs.

Abstract

The in vivo metabolism of 1-(3-mercapto-2-D-methyl-1-oxopropyl)-L-proline (SQ-14225) was investigated in rats and dogs. SQ-14225 labeled with 14C at the mercaptoacyl moiety was administered orally and the metabolites in the 24 hr urine were identified by comparing their Rf values with those of authentic samples. Unchanged SQ-14225 was trapped via its sulfhydryl group by the previous addition of N-ethylmaleimide to prevent air oxidation. In both animal species, most of the radioactivity was excreted as unchanged SQ-14225 and its disulfide (SQ-14551). A significant amount of the urinary radioactivity was accounted for by mixed disulfides, among which the disulfide with L-cysteine (Cys-SQ-14225) was predominant. N-Acetyl-Cys-SQ-14225 was also detected as a minor component, but the amount of the mixed disulfide with glutathione (GS-SQ-14225) was negligible. S-Methyl-SQ-14225 and its sulfoxide were also recognized. As judged from the negligible incorporation of radioactivity into collagen after administration of SQ-14225-3H labeled at the proline moiety, the metabolic cleavage of the amide bond in SQ-14225 was not significant.