Collect. Czech. Chem. Commun. 1991, 56, 2448-2455

Synthesis of pyridyl isosteres of thioperamide as H3-receptor histamine antagonists

C. Robin Ganellina, Dalia Jayesa, Yasmin S. Khalafa, Wasyl Tertiuka, Jean-Michel Arrangb, Nadia Defontaineb and Jean-Charles Schwartzb

a Department of Chemistry, University College London, Christopher Ingold Laboratories, 20 Gordon Street, London WC1H OAJ, England
b Unité 109 de Neurobiologie et Pharmacologie Centre Paul Broca de l’INSERM, 2 ter rue d’Alésia, Paris 75014, France


The synthesis and evaluation as H3-receptor histamine antagonists is described of novel isoteric analogues of thioperamide. The compounds are designed to have fewer NH groups in order to assist brain penetration. However none of the compounds is sufficiently active as an antagonist in vitro. The 2-pyridyl analogue II has Ki = 13 μmol 1-1.