http://www.cnr.it/ontology/cnr/individuo/prodotto/ID10234

Synthesis, labeling, and biological evaluation of halogenated 2 quinolinecarboxamides as potential radioligands for the visualization of peripheral benzodiazepine receptors (Articolo in rivista)

Type

Articolo in rivista (Classe)
Prodotto della ricerca (Classe)

Label

Synthesis, labeling, and biological evaluation of halogenated 2 quinolinecarboxamides as potential radioligands for the visualization of peripheral benzodiazepine receptors (Articolo in rivista) (literal)

Anno

2006-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1016/j.bmc.2006.02.004 (literal)

Alternative label

Cappelli A. 1, Matarrese M. 2, Moresco R.M. 2, Valenti S. 1, Anzini M. 1, Vomero S. 1, Turolla E.A. 2, Belloli S. 2, Simonelli P. 2, Filannino M.A. 2, Lecchi M. 3, Fazio F. 2 (2006)
Synthesis, labeling, and biological evaluation of halogenated 2 quinolinecarboxamides as potential radioligands for the visualization of peripheral benzodiazepine receptors
in Bioorganic & medicinal chemistry (Print)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Cappelli A. 1, Matarrese M. 2, Moresco R.M. 2, Valenti S. 1, Anzini M. 1, Vomero S. 1, Turolla E.A. 2, Belloli S. 2, Simonelli P. 2, Filannino M.A. 2, Lecchi M. 3, Fazio F. 2 (literal)

Pagina inizio

4055 (literal)

Pagina fine

4066 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#altreInformazioni

I.F. 2.286 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

14 (literal)

Rivista

Bioorganic & medicinal chemistry (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#descrizioneSinteticaDelProdotto

Sviluppo di nuove molecole per lo studio dei recettori delle benzodiazepine periferiche e loro potenziale applicazione come radiotraccianti in alternativa al PK-11195 (literal)

Note

ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

1. Dipartimento Farmaco Chimico Tecnologico and European Research Centre for Drug Discovery and Development, Università degli Studi, Siena, Italy 2. Istituto di Bioimmagini e Fisiologia Molecolare, CNR, Università di Milano-Bicocca, Istituto H. S. Raffaele, Milano, Italy 3. Istituto di Scienze Radiologiche, Università degli Studi, Milano, Italy (literal)

Titolo

Synthesis, labeling, and biological evaluation of halogenated 2 quinolinecarboxamides as potential radioligands for the visualization of peripheral benzodiazepine receptors (literal)

Abstract

The previous exploration of the structure-affinity relationships concerning 4-phenyl-2-quinolinecarboxamide peripheral benzodiazepine receptor (PBR) ligands 6 showed as an interesting result the importance of the presence of a chlorine atom in the methylene carbon at position 3 of the quinoline nucleus. The subnanomolar PBR affinity shown by N-benzyl-3-chloromethyl-N-methyl-4-phenyl-2-quinolinecarboxamide (6b) suggested its chlorine atom to be replaced with other halogens in order to optimize the interaction of the quinolinecarboxamide derivatives with PBR and to develop suitable candidates for positron emission tomography (PET) or single photon emission computed tomography (SPECT) studies. The binding studies led to the discovery of fluoromethyl derivative 6a, which showed an IC(50) value of 0.11nM and is, therefore, one of the most potent PBR ligands so far described. Fluoromethyl derivative 6a has been labeled with (11)C (t(1/2)=20.4min, beta(+)=99.8%) starting from the corresponding des-methyl precursor (14) using [(11)C]CH(3)I in the presence of tetrabutylammonium hydroxide in DMF with a 35-40% radiochemical yield (corrected for decay) and 1.5Ci/mumol of specific radioactivity. Ex vivo rat biodistribution and inhibition (following intravenous pre-administration of PK11195) studies showed that [(11)C]6a rapidly and specifically accumulated in PBR-rich tissues such as heart, lung, kidney, spleen, and adrenal, and at a lower level in other peripheral organs and in the brain. The images obtained in mouse with small animal YAP-(S)PET essentially confirmed the result of the ex vivo biodistribution experiments. The biological data suggest that [(11)C]6a is a promising radioligand for peripheral benzodiazepine receptor PET imaging in vivo. (literal)

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