title: Synthesis and biological evaluation of new oral carbapenems with 1-methyl-5-oxopyrrolidin-3-ylthio moiety.
abstract: The synthesis and biological properties of 1beta-methylcarbapenems with 1-methyl-5-oxopyrrolidin-3-ylthio group at the C-2 position were studied. The sodium (1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-methyl-2-[(R)-1-methyl-5-oxopyrro lidin-3-ylthio]-1-carbapen-2-em-3-carboxylate and its (S)-isomer at the 2-position show potent and well-balanced antibacterial activity. The pharmacokinetic parameters of the pivaloyloxymethyl esters of these two carbapenems were compared in mice. The in vivo potency of these carbapenems was compared with that of cefdinir. Good in vivo efficacy of these ester prodrugs reflected the high and prolonged blood levels in parent drugs achieved after oral administration to mice.
authors.affiliation: Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Kanno
authors.forename: M
authors.initials: M
authors.lastname: Miyauchi
authors.forename: T
authors.initials: T
authors.lastname: Shibayama
authors.forename: S
authors.initials: S
authors.lastname: Ohya
authors.forename: I
authors.initials: I
authors.lastname: Kawamoto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000627:therapeutic use; D019540:Area Under Curve; D001424:Bacterial Infections / Q000188:drug therapy*; D015780:Carbapenems / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077525:Cefdinir; D002511:Cephalosporins / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D015780:Carbapenems; D002511:Cephalosporins; D011355:Prodrugs; D000077525:Cefdinir