Pyrazolecarboxamide human neuropeptide Y5 receptor ligands with in vivo antifeedant activity.
1-Aryl-3-carboxamido-5-alkylpyrazoles were prepared based on a hit found in high-throughput screening of our corporate compound library in an assay measuring affinity for the human neuropeptide Y5 receptor. 1-(3-Trifluoromethylphenyl)-3-[N-(5-quinolinyl)carboxamido]-5-methylpyrazole (31) bound to the human neuropeptide Y5 receptor with a 80 nM IC(50 )and was shown to inhibit cumulative food consumption 43.2% 2-6 h after ip dosing in a fasting-induced feeding model in rats.
Kordik
C P
CP
Drug Discovery Division, The R. W. Johnson Pharmaceutical Research Institute, Welsh and McKean Roads, Spring House, PA 19477, USA. ckordik@pruis.jnj.com
Luo
C
C
Zanoni
B C
BC
Lovenberg
T W
TW
Wilson
S J
SJ
Vaidya
A H
AH
Crooke
J J
JJ
Rosenthal
D I
DI
Reitz
A B
AB
D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004435:Eating / Q000187:drug effects*; D005215:Fasting; D006801:Humans; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000737:chemistry* / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
C442372:1-(3-trifluoromethylphenyl)-3-((5-isoquinolinyl)carbonyl)-5-methylpyrazole; D007546:Isoquinolines; D008024:Ligands; D011720:Pyrazoles; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor