Syntheses and pharmacokinetic studies of prodrug esters for the development of oral carbapenem, L-084.
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.
Isoda
Takeshi
T
Medical Research Laboratories, Wyeth K.K., 1-6-34 Kashiwa-cho, Shiki-shi, Saitama 353-8511, Japan. isoda@konicaminolta.jp
Ushirogochi
Hideki
H
Satoh
Koichi
K
Takasaki
Tsuyoshi
T
Yamamura
Itsuki
I
Sato
Chisato
C
Mihira
Ado
A
Abe
Takao
T
Tamai
Satoshi
S
Yamamoto
Shigeki
S
Kumagai
Toshio
T
Nagao
Yoshimitsu
Y
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
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D004952:Esters; D011355:Prodrugs; C120999:L 084