title: Aminopyrazoles with high affinity for the human neuropeptide Y5 receptor.
abstract: 1,3-Disubstituted-5-aminopyrazoles were prepared based on a lead compound found through high-throughput screening of our corporate compound library in an assay measuring affinity for the human neuropeptide Y5 receptor. The target compounds were prepared by cyclization of alpha-cyanoketones with appropriate hydrazines, followed by reduction and coupling to various sulfonamido-carboxylic acids. Several of these arylpyrazoles (e.g., 19 and 45) displayed high affinity for the human NPY Y5 receptor (<20nM IC(50)s).
authors.affiliation: Drug Discovery Division, The R. W. Johnson Pharmaceutical Research Institute, Welsh and McKean Roads, Spring House, PA 19477, USA. ckordik@prius.jnj.com
authors.forename: C P
authors.initials: CP
authors.lastname: Kordik
authors.forename: C
authors.initials: C
authors.lastname: Luo
authors.forename: B C
authors.initials: BC
authors.lastname: Zanoni
authors.forename: S L
authors.initials: SL
authors.lastname: Dax
authors.forename: J J
authors.initials: JJ
authors.lastname: McNally
authors.forename: T W
authors.initials: TW
authors.lastname: Lovenberg
authors.forename: S J
authors.initials: SJ
authors.lastname: Wilson
authors.forename: A B
authors.initials: AB
authors.lastname: Reitz
mesh_terms: D001667:Binding, Competitive; D002460:Cell Line; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D011720:Pyrazoles / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C442371:5-amino-1-(3-trifluoromethylphenyl)-3-(((2-nitrophenylsulfonamido)methyl)phenyl)pyrazole; C442370:5-amino-1-(4-methylphenyl)-3-((4-methoxyphenylsulfonamido)phenyl)pyrazole; D011720:Pyrazoles; D017476:Receptors, Neuropeptide Y; D013449:Sulfonamides; C100568:neuropeptide Y5 receptor