title: Synthesis and in vitro activity of 1 beta-methyl C-2 quaternary heterocyclic alkylthio carbapenems.
abstract: 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.
authors.affiliation: Bristol-Myers Company, Pharmaceutical Research and Development Division, Wallingford, Connecticut 06492-7660.
authors.forename: C U
authors.initials: CU
authors.lastname: Kim
authors.forename: B Y
authors.initials: BY
authors.lastname: Luh
authors.forename: P F
authors.initials: PF
authors.lastname: Misco
authors.forename: J M
authors.initials: JM
authors.lastname: Hitchcock
mesh_terms: 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
chemical_list: D013845:Thienamycins; D004150:Dipeptidases