FR-104007

WS1358A1, a novel inhibitor of renal dehydropeptidase (DHP), augmented the urinary recovery of a carbapenem antibiotic imipenem and improved its protective effect in experimental infections when simultaneously administered to mice with the antibiotic. WS1358A1 was a competitive DHP inhibitor with a Ki value of 1.6 x 10(-7) M.

The structures of WS1358A1 and B1, new dehydropeptidase inhibitors isolated from Streptomyces parvulus subsp. tochigiensis No. 1358, have been established to be 2-hydroxy-2-hydroxyaminocarbonyl-3-methylglutaric acid (1) and 2-hydroxy-2-hydroxyaminocarbonylglutaric acid (2), respectively, on the basis of spectroscopic evidence and synthesis of the racemates.