Document Report Card

ID: ALA1128413

Journal: J Med Chem

Title: The serotonin 5-HT4 receptor. 1. Design of a new class of agonists and receptor map of the agonist recognition site.

Authors: Buchheit KH, Gamse R, Giger R, Hoyer D, Klein F, Klöppner E, Pfannkuche HJ, Mattes H.

Abstract: The design and synthesis of a new class of potent and selective 5-HT4 receptor agonists containing an indole nucleus linked to a carbazimidamide are presented. A conformational study of the 5-HT4 receptor agonists serotonin and zacopride led to the identification of an initial pharmacophore and to the definition of a three-dimensional map of the 5-HT4 agonist recognition site. 1, a representative member of our new class of 5-HT4 receptor agonists, incorporates all reference structural features and matched perfectly with these models. 1 is a highly potent, full agonist at 5-HT4 receptors present in the isolated electrically stimulated guinea pig ileum preparation, with a pD2 value of 8.8, displaying selectivity (ranging from 40- to over 10,000-fold) versus other members of the serotonin receptor family.

CiteXplore: 7608898

DOI: 10.1021/jm00013a009