Synthesis of Linezolid Metabolites PNU-142300 and PNU-142586 toward the Exploration of Metabolite-Related Events.
Linezolid (1) is an oxazolidinone antibiotic that is partially metabolized in vivo via ring cleavage of its morpholine moiety to mainly form two metabolites, PNU-142300 (2) and PNU-142586 (3). It is supposed that accumulation of 2 and 3 in patients with renal insufficiency may cause thrombocytopenia, one of the adverse effects of linezolid. However, the poor availability of 2 and 3 has hindered further investigation of the clinical significance of the accumulation of these metabolites. In this paper, we synthesized metabolites 2 and 3 via a common synthetic intermediate, 4; this will encourage further exploration of events related to these metabolites and lead to improved clinical use of linezolid.
Faculty of Pharmacy, Keio University.
Kengo
K
Hanaya
Kazuaki
K
Matsumoto
Yuta
Y
Yokoyama
Junko
J
Kizu
Mitsuru
M
Shoji
Takeshi
T
Sugai
D000069349:Linezolid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism*
C000614931:PNU-142300; C000614932:PNU-142586; D000069349:Linezolid