Synthesis and evaluation of N-(5-methyl-3-oxo-1,2-diphenyl-2,3-dihydro-1H- pyrazol-4-yl)-N′-phenylureas as cholecystokinin antagonists

Eric Lattmann*, Jintana Sattayasai, Yodchai Boonprakob, Pornthip Lattmann, Harjit Singh

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

In the search for new cholecystokinin (CCK) ligands, ureidopyrazolines were identified in combinatorial libraries using 168 chemically diverse amines. The structure-activity relationship optimisation of this pyrazoline template 4a resulted in novel 3-oxo-1,2-diphenyl-2,3-dihydro-1H-pyrazol-4-yl)-N′- phenylureas 5a-5o. These novel CCK ligands have shown to act as mixed CCK-A/CCK-B ligands in a [125]I-CCK-8 receptor binding assay. The best pyrazoline 5e of this series displayed an IC 50 of 20 and 25 nmol/L for the CCK-A, and CCK-B receptor, respectively. In a subsequent in vivo evaluation using various behavior pharmacological assays, an anxiolytic effect of these novel diphenylpyrazolinyl ureas was found in the elevated x-maze with an ED 50 of 1.7 mg/kg. In the despair swimming test, a model for testing antidepressants, an ED 50 of 0.69 mg/kg was determinated for urea 5e and the antidepressant effect had a magnitude comparable to desimipramine.

Original languageEnglish
Pages (from-to)251-258
Number of pages8
JournalArzneimittelforschung
Volume55
Issue number5
Publication statusPublished - 17 Jun 2005

Keywords

  • cholecystokinin
  • mixed antagonists
  • 3-oxo-1
  • 2-diphenyl-2
  • 3-dihydro-1H-pyrazol-4-y1)-N `-phenylureas
  • cholecystokinin antagonism
  • in vivo studies
  • mouse
  • synthesis

Fingerprint Dive into the research topics of 'Synthesis and evaluation of N-(5-methyl-3-oxo-1,2-diphenyl-2,3-dihydro-1H- pyrazol-4-yl)-N′-phenylureas as cholecystokinin antagonists'. Together they form a unique fingerprint.

  • Cite this