Synthesis of new thiophene and benzo[b]thiophene hydrazide derivatives as human NPY Y(5) antagonists

Silvia Galiano; Oihana Erviti; Silvia Pérez; Antonio Moreno; Laura Juanenea; Ignacio Aldana; Antonio Monge

doi:10.1016/j.bmcl.2003.11.070

Synthesis of new thiophene and benzo[b]thiophene hydrazide derivatives as human NPY Y(5) antagonists

Bioorg Med Chem Lett. 2004 Feb 9;14(3):597-9. doi: 10.1016/j.bmcl.2003.11.070.

Authors

Silvia Galiano¹, Oihana Erviti, Silvia Pérez, Antonio Moreno, Laura Juanenea, Ignacio Aldana, Antonio Monge

Affiliation

¹ Unidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada (CIFA), Universidad de Navarra, c/Irunlarrea s/n, 31080 Pamplona, Spain.

PMID: 14741250
DOI: 10.1016/j.bmcl.2003.11.070

Abstract

Neuropeptide Y is one of the most potent appetite stimulating hormones known. Novel thiophene and benzo[b]thiophene hydrazide derivatives were synthetized and evaluated biologically as NPY Y(1) and Y(5) receptor subtype antagonists. They were found to have nanomolar binding affinities for human NPY Y(5) receptor, obtaining the lead compound, trans-N-4-[N'-(thiophene-2-carbonyl)hydrazinocarbonyl]cyclohexylmethyl-4-bromobenzenesulfonamide, which binds with a 7.70 nM IC(50) to the hY(5) receptor.

MeSH terms

Animals
Binding Sites
COS Cells
Chlorocebus aethiops
Humans
Molecular Structure
Receptors, Neuropeptide Y / antagonists & inhibitors*
Structure-Activity Relationship
Thiophenes / chemical synthesis*
Thiophenes / pharmacology*

Substances

Receptors, Neuropeptide Y
Thiophenes
neuropeptide Y-Y1 receptor
neuropeptide Y5 receptor
benzothiophene