Synthesis and biological activity of some known and putative duloxetine metabolites

F Kuo; T A Gillespie; P Kulanthaivel; R J Lantz; T W Ma; D L Nelson; P G Threlkeld; W J Wheeler; P Yi; M Zmijewski

doi:10.1016/j.bmcl.2004.04.066

Synthesis and biological activity of some known and putative duloxetine metabolites

Bioorg Med Chem Lett. 2004 Jul 5;14(13):3481-6. doi: 10.1016/j.bmcl.2004.04.066.

Authors

F Kuo¹, T A Gillespie, P Kulanthaivel, R J Lantz, T W Ma, D L Nelson, P G Threlkeld, W J Wheeler, P Yi, M Zmijewski

Affiliation

¹ Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285 USA. [email protected]

PMID: 15177457
DOI: 10.1016/j.bmcl.2004.04.066

Abstract

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.

Publication types

Comparative Study

MeSH terms

Adrenergic Uptake Inhibitors / chemical synthesis*
Adrenergic Uptake Inhibitors / metabolism
Adrenergic Uptake Inhibitors / pharmacology
Binding Sites
Cloning, Molecular
Dopamine Plasma Membrane Transport Proteins
Duloxetine Hydrochloride
Glucuronides / metabolism
Humans
Membrane Glycoproteins / metabolism
Membrane Transport Proteins / metabolism
Models, Chemical
Nerve Tissue Proteins / metabolism
Radioligand Assay
Sulfates / metabolism
Thiophenes / chemical synthesis*
Thiophenes / metabolism
Thiophenes / pharmacology

Substances

Adrenergic Uptake Inhibitors
Dopamine Plasma Membrane Transport Proteins
Glucuronides
Membrane Glycoproteins
Membrane Transport Proteins
Nerve Tissue Proteins
Sulfates
Thiophenes
Duloxetine Hydrochloride