新規経口性ペネムβ-ラクタム抗菌薬 : ファロムの創製

概要

論文の詳細を見る
An orally active penem antibiotic, Farm(generic name : faropenem), was designed by the conformational analysis of active and inactive penem derivatives. Faropenem showed potent activity against a wide variety of bacteria including extnded-spectrum β-lactamase(ESBL)-producing ones. The mechanism of the stability against ESBL was elucidated by modeling the Michaelis complex of faropenem and Toho-1, an ESBL. Modeling of a complex of faropenem at the active site of a penicillin-binding protein 2(PBP2) model suggested the characteristic affinity for faropenem with PBP2 of Escherichia coli. Faropenem has been totally synthesized from (R)-1, 3-butanediol. The synthetic intermediate, a 3-hydroxyethyl-4-acetoxyazetidinone derivative, was efficiently prepared by the 2+2 coupling of a optically active vinylsulfide derivative and chlorosulfonyl isocyanate, followed by the substitution of the acetoxy group for the thiophenyl group at the C-4 position.
社団法人日本薬学会の論文
2001-12-01