Aminopyrazoles with high affinity for the human neuropeptide Y5 receptor

C P Kordik; C Luo; B C Zanoni; S L Dax; J J McNally; T W Lovenberg; S J Wilson; A B Reitz

doi:10.1016/s0960-894x(01)00448-6

Aminopyrazoles with high affinity for the human neuropeptide Y5 receptor

Bioorg Med Chem Lett. 2001 Sep 3;11(17):2283-6. doi: 10.1016/s0960-894x(01)00448-6.

Authors

C P Kordik¹, C Luo, B C Zanoni, S L Dax, J J McNally, T W Lovenberg, S J Wilson, A B Reitz

Affiliation

¹ Drug Discovery Division, The R. W. Johnson Pharmaceutical Research Institute, Welsh and McKean Roads, Spring House, PA 19477, USA. ckordik@prius.jnj.com

PMID: 11527715
DOI: 10.1016/s0960-894x(01)00448-6

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).

MeSH terms

Binding, Competitive
Cell Line
Drug Design
Drug Evaluation, Preclinical
Humans
Inhibitory Concentration 50
Pyrazoles / chemistry*
Pyrazoles / metabolism*
Pyrazoles / pharmacology
Receptors, Neuropeptide Y / drug effects
Receptors, Neuropeptide Y / metabolism*
Structure-Activity Relationship*
Sulfonamides / chemistry*
Sulfonamides / metabolism*
Sulfonamides / pharmacology

Substances

5-amino-1-(3-trifluoromethylphenyl)-3-(((2-nitrophenylsulfonamido)methyl)phenyl)pyrazole
5-amino-1-(4-methylphenyl)-3-((4-methoxyphenylsulfonamido)phenyl)pyrazole
Pyrazoles
Receptors, Neuropeptide Y
Sulfonamides
neuropeptide Y5 receptor