Inhibition of the mammalian. beta.-lactamase renal dipeptidase (dehydropeptidase-I) by Z-2-(acylamino)-3-substituted-propenoic acids

DW Graham, WT Ashton, L Barash…

Index: Graham, Donald W.; Ashton, Wallace T.; Barash, Louis; Brown, Jeannette E.; Brown, Ronald D.; et al. Journal of Medicinal Chemistry, 1987 , vol. 30, # 6 p. 1074 - 1090

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Citation Number: 85

Abstract

The title enzyme deactivates the potent carbapenem antibiotic imipenem in the kidney, producing low antibiotic levels in the urinary tract. A series of (Z)-2-(acylamino)-3-substituted- propenoic acids (3) are specific, competitive inhibitors of the enzyme capable of increasing the urinary concentration of imipenem in vivo. Many of the compounds were prepared in one step from an a-keto acid and a primary amide. The optimum R2 groups are 2, 2-dimethyl,- ...