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rdf:type |
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lifeskim:mentions |
umls-concept:C0013030,
umls-concept:C0032743,
umls-concept:C0035647,
umls-concept:C0047550,
umls-concept:C0220781,
umls-concept:C0220825,
umls-concept:C0597357,
umls-concept:C1515655,
umls-concept:C1522485,
umls-concept:C1707689,
umls-concept:C1708632,
umls-concept:C1883254,
umls-concept:C2347885
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pubmed:issue |
20
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pubmed:dateCreated |
2010-10-21
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pubmed:abstractText |
Here we describe the design, synthesis, and evaluation of physicochemical and pharmacological properties of D(4) dopamine receptor ligands related to N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (2). Structural features were incorporated to increase affinity for the target receptor, to improve selectivity over D(2) and ?(1) receptors, to enable labeling with carbon-11 or fluorine-18, and to adjust lipophilicity within the range considered optimal for brain penetration and low nonspecific binding. Compounds 7 and 13 showed the overall best characteristics: nanomolar affinity for the D(4) receptor, >100-fold selectivity over D(2) and D(3) dopamine receptors, 5-HT(1A), 5-HT(2A), and 5-HT(2C) serotonin receptors and ?(1) receptors, and log?P = 2.37-2.55. Following intraperitoneal administration in mice, both compounds rapidly entered the central nervous system. The methoxy of N-[2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl]-3-methoxybenzamide (7) was radiolabeled with carbon-11 and subjected to PET analysis in non-human primate. [(11)C]7 time-dependently accumulated to saturation in the posterior eye in the region of the retina, a tissue containing a high density of D(4) receptors.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:BerardiFrancescoF,
pubmed-author:CacciaSilvioS,
pubmed-author:De GiorgioPaolaP,
pubmed-author:FracassoClaudiaC,
pubmed-author:HiguchiMakotoM,
pubmed-author:LacivitaEnzaE,
pubmed-author:LeeIrene TIT,
pubmed-author:LeopoldoMarcelloM,
pubmed-author:MaedaJunJ,
pubmed-author:PerroneRobertoR,
pubmed-author:RodeheaverSean ISI,
pubmed-author:SchetzJohn AJA,
pubmed-author:SuharaTetsuyaT,
pubmed-author:WeissBryan ABA,
pubmed-author:ZhangMing-RongMR
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pubmed:issnType |
Electronic
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pubmed:day |
28
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pubmed:volume |
53
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7344-55
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pubmed:dateRevised |
2011-10-28
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pubmed:meshHeading |
pubmed-meshheading:20873719-Animals,
pubmed-meshheading:20873719-Benzamides,
pubmed-meshheading:20873719-Brain,
pubmed-meshheading:20873719-Carbon Radioisotopes,
pubmed-meshheading:20873719-Cell Line,
pubmed-meshheading:20873719-Humans,
pubmed-meshheading:20873719-Isotope Labeling,
pubmed-meshheading:20873719-Ligands,
pubmed-meshheading:20873719-Macaca mulatta,
pubmed-meshheading:20873719-Male,
pubmed-meshheading:20873719-Mice,
pubmed-meshheading:20873719-Nitriles,
pubmed-meshheading:20873719-Piperazines,
pubmed-meshheading:20873719-Positron-Emission Tomography,
pubmed-meshheading:20873719-Pyridines,
pubmed-meshheading:20873719-Radioligand Assay,
pubmed-meshheading:20873719-Radiopharmaceuticals,
pubmed-meshheading:20873719-Rats,
pubmed-meshheading:20873719-Rats, Sprague-Dawley,
pubmed-meshheading:20873719-Receptors, Dopamine D4,
pubmed-meshheading:20873719-Retina,
pubmed-meshheading:20873719-Structure-Activity Relationship,
pubmed-meshheading:20873719-Tissue Distribution
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pubmed:year |
2010
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pubmed:articleTitle |
Design, synthesis, radiolabeling, and in vivo evaluation of carbon-11 labeled N-[2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl]-3-methoxybenzamide, a potential positron emission tomography tracer for the dopamine D(4) receptors.
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pubmed:affiliation |
Dipartimento Farmaco-Chimico, Universita? degli Studi di Bari A Moro, Via Orabona 4, 70125 Bari, Italy.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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