Synthesis and in vitro activity of 1 beta-methyl C-2 quaternary heterocyclic alkylthio carbapenems.
New 1 beta-methylcarbapenems having various (substituted) quaternary heterocyclic alkythio groups at the C-2 position were synthesized and tested for antibacterial activity and renal dipeptidase susceptibility. Compounds having the 1 beta-methyl substituent were found to possess an increased stability to the enzyme. In addition, combination of the 1 beta-methyl substituent and the C-2 quaternary heterocyclic alkylthio side chain generated compounds with excellent antipseudomonal activity and improved stability toward hydrolysis by renal dipeptidase.
Kim
C U
CU
Bristol-Myers Company, Pharmaceutical Research and Development Division, Wallingford, Connecticut 06492-7660.
Luh
B Y
BY
Misco
P F
PF
Hitchcock
J M
JM
D055598:Chemical Phenomena; D002621:Chemistry; D004150:Dipeptidases / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006868:Hydrolysis; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D013845:Thienamycins / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D013845:Thienamycins; D004150:Dipeptidases