title: BIIE0246: a selective and high affinity neuropeptide Y Y(2) receptor antagonist.
abstract: The in vitro biological characterisation of the first potent and selective non-peptide neuropeptide Y Y(2) receptor antagonist, (S)-N(2)-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b, e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl] cylopentyl] acetyl]-N-[2-[1,2-dihydro-3,5(4H)-dioxo-1,2-diphenyl-3H-1,2, 4-triazol-4-yl]ethyl]-argininamid (BIIE0246) is reported. BIIE0246 displaced [125I]neuropeptide Y with high affinity (IC(50)=3.3 nM) from the human neuropeptide Y Y(2) receptor and proved to be highly selective. BIIE0246 displayed antagonistic properties and thus represents the first selective non-peptide neuropeptide Y Y(2) receptor antagonist.
authors.affiliation: Boehringer Ingelheim Pharma, Birkendorfer Str. 65, D-88397, Biberach, Germany. henri.doods@bc.boehringer-ingelheim.com
authors.forename: H
authors.initials: H
authors.lastname: Doods
authors.forename: W
authors.initials: W
authors.lastname: Gaida
authors.forename: H A
authors.initials: HA
authors.lastname: Wieland
authors.forename: H
authors.initials: H
authors.lastname: Dollinger
authors.forename: G
authors.initials: G
authors.lastname: Schnorrenberg
authors.forename: F
authors.initials: F
authors.lastname: Esser
authors.forename: W
authors.initials: W
authors.lastname: Engel
authors.forename: W
authors.initials: W
authors.lastname: Eberlein
authors.forename: K
authors.initials: K
authors.lastname: Rudolf
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D001552:Benzazepines / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
chemical_list: D001552:Benzazepines; D007457:Iodine Radioisotopes; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D001120:Arginine; C403256:BIIE 0246