Giuliani G. 1, Cappelli A. 1, Matarrese M. 2,3, Masiello V. 2,3, Turolla E.A. 2,3, Monterisi C. 2,3, Fazio F. 3, Anzini M. 1, Pericot Mohr G.L. 1, Riitano D. 3, Finetti F. 4, Morbidelli L. 4, Ziche M. 4, Giorgi G. 5, Vomero S. 1
1. Dipartimento Farmaco Chimico Tecnologico and European Research Centre for Drug Discovery and Development, Università degli Studi di Siena, Siena. 2. CNR-Istituto di Bioimmagini e Fisiologia Molecolare, Segrate (MI) 3. Università di Milano/Bicocca, Istituto Scientifico S. Raffaele, Milano. 4. Dipartimento di Farmacologia, Istituto Superiore di Sanità, Roma. 5. Sezione di Farmacologia, Dipartimento di Biotecnologie, Università degli Studi di Siena, Siena. 6. Dipartimento di Chimica, Università degli Studi di Siena, Siena.
The quinoline nucleus of the previously described 4-phenylquinoline-3-carboxamides NK(1) receptor ligands 7 has been transformed into either substituted or azole-(i.e., triazole or tetrazole) fused pyridine moieties of compounds 9 and 10, respectively, in order to obtain NK(1) receptor ligands showing lower molecular weight or higher hydrophilicity. The program of molecular manipulations produced NK(1) receptor ligands showing affinity in the nanomolar range. In particular, 4-methyl-1-piperazinyl derivative 9j showed an IC(50) value of 4.8nM and was proved to behave as a NK(1) antagonist blocking Sar(9)-SP-sulfone induced proliferation and migration of microvascular endothelial cells. Therefore, compound 9j has been labeled with [(11)C]CH(3)I (t(1/2)=20.4min, ²(+)=99.8%) starting from the corresponding des-methyl precursor 9i using with a radiochemical yield of about 10% (not decay corrected) and a specific radioactivity>1Ci/¼mol in order to be used as a radiotracer in next PET studies.
Bioorganic & medicinal chemistry (Print) 19 , pp. 2242–2251
NK1 receptor, Synthesis, Radiolabelling
Masiello Valeria, Turolla Elia Anna, Monterisi Cristina, Matarrese Mario
ID: 10528
Year: 2011
Type: Articolo in rivista
Creation: 2011-03-23 00:00:00.000
Last update: 2011-06-30 00:00:00.000
External IDs
CNR OAI-PMH: oai:it.cnr:prodotti:10528