BIIE0246: a selective and high affinity neuropeptide Y Y(2) receptor antagonist.
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.
Doods
H
H
Boehringer Ingelheim Pharma, Birkendorfer Str. 65, D-88397, Biberach, Germany. henri.doods@bc.boehringer-ingelheim.com
Gaida
W
W
Wieland
H A
HA
Dollinger
H
H
Schnorrenberg
G
G
Esser
F
F
Engel
W
W
Eberlein
W
W
Rudolf
K
K
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
D001552:Benzazepines; D007457:Iodine Radioisotopes; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D001120:Arginine; C403256:BIIE 0246