Synthesis and biological activity of some known and putative duloxetine metabolites.
Several putative phase I duloxetine metabolites, 4-hydroxy-, 5-hydroxy-, 6-hydroxy-, 5-hydroxy-6-methoxy-, 6-hydroxy-5-methoxy-, 5,6-dihydroxy-, and 4,6-dihydroxyduloxetine were synthesized, and their phase II metabolite as glucuronide or sulfate conjugates were also synthesized. Their in vitro binding activities were compared to that of parent compound duloxetine.
Kuo
F
F
Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285 USA. kuo_fengjiun@lilly.com
Gillespie
T A
TA
Kulanthaivel
P
P
Lantz
R J
RJ
Ma
T W
TW
Nelson
D L
DL
Threlkeld
P G
PG
Wheeler
W J
WJ
Yi
P
P
Zmijewski
M
M
D018759:Adrenergic Uptake Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D003001:Cloning, Molecular; D050483:Dopamine Plasma Membrane Transport Proteins; D000068736:Duloxetine Hydrochloride; D020719:Glucuronides / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008956:Models, Chemical; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011869:Radioligand Assay; D013431:Sulfates / Q000378:metabolism; D013876:Thiophenes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D050483:Dopamine Plasma Membrane Transport Proteins; D020719:Glucuronides; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D013431:Sulfates; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride