Linked Life Data

8496936

Source:http://linkedlifedata.com/resource/pubmed/id/8496936

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1993-6-24
pubmed:abstractText
2-, 3-, and 4-idophenyl derivatives of the high-affinity sigma ligand N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (1) were synthesized in two to four steps starting from N-methyl-2-(1-pyrrolidinyl)ethylamine. These compounds were evaluated for their capacity to label both sigma 1 and sigma 2 subtypes in vitro. sigma-1 binding affinity was determined by measuring competition with [3H]-(+)-pentazocine binding to guinea pig brain membranes while sigma 2 binding was evaluated through competition with [3H]DTG binding to rat liver membranes in the presence of excess dextrallorphan. The binding data revealed that N-[2-(3-iodophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (2) and N-[2-(4-iodophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (3) displayed almost identical binding affinity at sigma 1 sites to the parent compound 1. This suggests that the 3- or 4-iodo group can effectively substitute for the 3,4-dichloro substituents of 1. In this series of compounds, Ki's at the sigma 1 site varied from 2.0 nM for N-(4-iodobenzyl)-N-methyl-2-(1-pyrrolidinyl)ethylamine (6) to 26.6 nM for N-(2-iodobenzyl)-N-methyl-2-(1-pyrrolidinyl)ethylamine (4). Ki's for sigma 2 site ranged from 8.1 nM for 1 to 220 nM for N-(3-bromobenzyl)-N-methyl-2-(1-pyrrolidinyl)ethylamine (11) while the sigma 2/sigma 1 ratio varied from 1.8 for 4 to 25 for 11. Comparing halogen substitution, the trend Cl = I > Br > F was observed for binding affinity at sigma 1 sites; no such trend was observed at sigma 2 sites. On the basis of the binding data, compounds 2 and 3 were selected for labeling with 123I. Thus, treatment of the corresponding 3- and 4-(tributylstannyl) intermediates (7 and 8) with Na123I in the presence of excess CH3CO3H furnished [123I]-2 and [123I]-3 in up to 70% radiochemical yield. Preliminary in vitro binding with [123I]-3 indicated up to 97% specific binding with guinea pig brain membranes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
566-71
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8496936-Animals, pubmed-meshheading:8496936-Binding, Competitive, pubmed-meshheading:8496936-Binding Sites, pubmed-meshheading:8496936-Brain, pubmed-meshheading:8496936-Bromine, pubmed-meshheading:8496936-Cell Membrane, pubmed-meshheading:8496936-Chlorides, pubmed-meshheading:8496936-Ethylenediamines, pubmed-meshheading:8496936-Fluorine, pubmed-meshheading:8496936-Guinea Pigs, pubmed-meshheading:8496936-Iodine, pubmed-meshheading:8496936-Iodine Radioisotopes, pubmed-meshheading:8496936-Iodobenzenes, pubmed-meshheading:8496936-Ligands, pubmed-meshheading:8496936-Liver, pubmed-meshheading:8496936-Male, pubmed-meshheading:8496936-Molecular Structure, pubmed-meshheading:8496936-Pentazocine, pubmed-meshheading:8496936-Pyrrolidines, pubmed-meshheading:8496936-Rabbits, pubmed-meshheading:8496936-Receptors, sigma, pubmed-meshheading:8496936-Structure-Activity Relationship, pubmed-meshheading:8496936-Tomography, Emission-Computed, Single-Photon
pubmed:year
1993
pubmed:articleTitle
Synthesis and binding characteristics of potential SPECT imaging agents for sigma-1 and sigma-2 binding sites.
pubmed:affiliation
Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't