title: Syntheses and pharmacokinetic studies of prodrug esters for the development of oral carbapenem, L-084.
abstract: We discovered an orally active carbapenem, L-084, through pharmacokinetic studies on various prodrug esters of (1R,5S,6S)-6-[(R)-1-hydroxyethyl]-l-methyl-2-[1-(1,3-thiazolin-2-yl)azetidin-3-yl]thio-1-carbapen-2-em-3-carboxylic acid (LJC11,036). L-084 showed a strong antimicrobial activity against Gram-positive and Gram-negative bacteria and exhibited the highest intestinal absorption among synthesized prodrugs of LJC11,036.
authors.affiliation: Medical Research Laboratories, Wyeth K.K., 1-6-34 Kashiwa-cho, Shiki-shi, Saitama 353-8511, Japan. isoda@konicaminolta.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Isoda
authors.forename: Hideki
authors.initials: H
authors.lastname: Ushirogochi
authors.forename: Koichi
authors.initials: K
authors.lastname: Satoh
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takasaki
authors.forename: Itsuki
authors.initials: I
authors.lastname: Yamamura
authors.forename: Chisato
authors.initials: C
authors.lastname: Sato
authors.forename: Ado
authors.initials: A
authors.lastname: Mihira
authors.forename: Takao
authors.initials: T
authors.lastname: Abe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tamai
authors.forename: Shigeki
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumagai
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Nagao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D015780:Carbapenems / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D004952:Esters; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D004952:Esters; D011355:Prodrugs; C120999:L 084