Pyrido[2,3-d]pyrimidine Antibacterial Agents. IV. Synthesis of Metabolites of Piromidic Acid

Abstract

Three metabolites of the antibacterial agent, piromidic acid (8-ethyl-5,8-dihydro-5-oxo-2-(l-pyrrolidinyl)pyrido[2,3-d]pyrimidine-6-carboxylic acid), were synthesized in order to confirm their structures, i.e., 2-(3-hydroxy-1-pyrrolidinyl)-(4), 2-(2-hydroxy-1-pyrrolidinyl)-(8), and 2-(3-carboxypropylamino)-8-ethyl-5,8-dihydro-5-oxopyrido[2,3-d]-pyrimidine-6-carboxylic acids (13). Compounds 4, 8, and 13 were identified with the metabolites designated as A, B, and I, respectively, on the basis of their IR, UV, MS, and NMR spectra. 8-Ethyl-5,8-dihydro-2-(3- and 4-hydroxypiperidino)-5-oxopyrido[2,3-d]pyrimidine-6-carboxylic acids (6a and 6b) as well as the O-formyl (5a), -acetyl (5b), -benzoyl (5c), and -methanesulfonyl (5d) derivatives of 4 were prepared and tested for antibacterial activity. Of the compounds discussed in this paper, 4 was the most active, particularly against gram-negative bacteria. © 1980, The Pharmaceutical Society of Japan. All rights reserved.