Beta-Lactam antibiotics derived from nitrogen heterocyclic acetic acids. 1. Penicillin derivatives

In an attempt to synthesize antibacterial agents effective against gram-negative bacteria, penicillin derivatives were prepared from substituted and unsubstituted 1,4-dihyro-2-oxopyridine-1-acetic acids, 1,4-dihydro-4-oxopyridine-1-acetic acids, and 1,2,3,4-tetrahydro-2,4-dioxopyrimidine-1-acetic acids. The unsubstituted derivatives displayed moderate activity against gram-negative bacteria; however, substitution (alkyl, chloro, nitro, acetyl, and cyano) on the heterocyclic ring of these acetic acids and (alkyl, phenyl) in the alpha position decreased the activity of the penicillin derivatives against gram-negative organisms.