title: Non-peptide NK1 receptor ligands based on the 4-phenylpyridine moiety.
abstract: 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 4.8 nM 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)=20.4 min, β(+)=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>1 Ci/μmol in order to be used as a radiotracer in next PET studies.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico and European Research Centre for Drug Discovery and Development, Università degli Studi di Siena, Via A. Moro, 53100 Siena, Italy.
authors.forename: Germano
authors.initials: G
authors.lastname: Giuliani
authors.forename: Andrea
authors.initials: A
authors.lastname: Cappelli
authors.forename: Mario
authors.initials: M
authors.lastname: Matarrese
authors.forename: Valeria
authors.initials: V
authors.lastname: Masiello
authors.forename: Elia Anna
authors.initials: EA
authors.lastname: Turolla
authors.forename: Cristina
authors.initials: C
authors.lastname: Monterisi
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Fazio
authors.forename: Maurizio
authors.initials: M
authors.lastname: Anzini
authors.forename: Galla
authors.initials: G
authors.lastname: Pericot Mohr
authors.forename: Daniela
authors.initials: D
authors.lastname: Riitano
authors.forename: Federica
authors.initials: F
authors.lastname: Finetti
authors.forename: Lucia
authors.initials: L
authors.lastname: Morbidelli
authors.forename: Marina
authors.initials: M
authors.lastname: Ziche
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giorgi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Vomero
mesh_terms: D000577:Amides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002250:Carbon Radioisotopes / Q000737:chemistry; D002417:Cattle; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D042783:Endothelial Cells / Q000187:drug effects; D007553:Isotope Labeling; D008024:Ligands; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D018040:Receptors, Neurokinin-1 / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D002250:Carbon Radioisotopes; D008024:Ligands; D011725:Pyridines; D018040:Receptors, Neurokinin-1; C051448:4-phenylpyridine