Abstract:
:In order to develop selective radioactive ligands for the study of presynaptic monoamine uptake sites, iodinated derivatives of tomoxetine were synthesized and evaluated in radioligand binding assays. Iodotomoxetine derivatives showed high affinity for serotonin (5-HT) uptake sites using a rat cortical membrane preparation. Compound 1R,(R)-(-)-N-methyl-3-(4-iodo-2-methylphenoxy)-3-phenylpropanamine , was the most potent and showed high stereoselectivity for 5-HT uptake sites (Ki, R isomer = 0.65 nM, S isomer = 13.9 nM). Changing the position of the methyl group or eliminating the methyl group at the phenoxy ring resulted in a loss of stereoselectivity. Substitution of the methyl group of tomoxetine with iodine gave the R and S isomers of N-methyl-3-(2-iodophenoxy)-3-phenylpropanamine 4R and 4S. These compounds displayed stereoselectivity for the norepinephrine (NE) (Ki values = 0.24 and 9.35 nM for R and S isomers, respectively). The in vitro binding data suggest that 1R and 4R are potential radioiodinated ligands for pharmacological studies of 5-HT and NE uptake sites, respectively.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Chumpradit S,Kung MP,Panyachotipun C,Prapansiri V,Foulon C,Brooks BP,Szabo SA,Tejani-Butt S,Frazer A,Kung HFdoi
10.1021/jm00101a029keywords:
subject
Has Abstractpub_date
1992-11-13 00:00:00pages
4492-7issue
23eissn
0022-2623issn
1520-4804journal_volume
35pub_type
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