Use of amino acid N-carboxy anhydride in the synthesis of peptide prodrug derivatives (including beta-chloroalanyl) of C4-beta-aminoalkyl carbapenems. In vitro and in vivo activities.
Mono- and dipeptide derivatives of C4-beta-aminoalkyl carbapenems were synthesized by the use of amino acid N-carboxy anhydride for the peptide bond formation. They were shown to act as prodrugs in vivo while imparting the much desired chemical stability. The beta-chloroalanyl derivative was suggested to act, in part, as a "dual-purpose" antibacterial.
Rao
V S
VS
Bristol-Myers Squibb Pharmaceutical Research Institute, Candiac, Qc, Canada.
Fung-Tomc
J C
JC
Desiderio
J V
JV
D000596:Amino Acids / Q000138:chemical synthesis*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D015780:Carbapenems / Q000138:chemical synthesis* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000138:chemical synthesis*; D011355:Prodrugs / Q000138:chemical synthesis*; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D015780:Carbapenems; D009842:Oligopeptides; D011355:Prodrugs; D015091:beta-Alanine; C006977:3-chloroalanine