A Qualitative Model for the Histamine H3 Receptor Explaining Agonistic and Antagonistic Activity Simultaneously

4-Benzyl-1H-imidazoles with Oxazoline Termini as Histamine H3 Receptor Agonists

“…More specifically, the interaction of the agonists with D114 is suggested to have a pronounced effect on the conformation of this residue, which has already been associated with receptor activation. 28 Receptor Selectivity and Cytochrome P 450 Binding. The three high-affinity ligands 17, 18, and 26 were evaluated further for their selectivity on the full panel of histamine receptors.…”

“…Starting from two HTS hits (10 and 11, Scheme 2), the side chain was systematically altered with predominantly lipophilic substituents (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). This exercise has not only afforded several novel H 3 R agonists with affinities and activities in the single digit nM range but has also provided molecular clues on how agonists without a basic side chain are able to activate H 3 R. Last, our results also reveal a hitherto unexplored functional group in H 3 R research.…”

Molecular modeling and QSAR-based design of histamine receptor ligands

“…A pharmacophore model explaining antagonistic and agonistic effects of ligands at the H 3 R was derived [55]. 'Receptor'-pharmacon complexes were constructed by mimicking the highly conserved Asp3.32 114 , playing a central role in ligand binding, by propionic acid.…”

Three-dimensional models of histamine H3 receptor antagonist complexes and their pharmacophore

“…This approach has been particularly successful for investigating GPCR/ligand binding modes and is complementary to 3D receptor/ligand modelling [30]. Consequently, two papers describing pharmacophore models of H 3 receptor antagonists have been published [31,32]. In both studies only imidazole based antagonists were considered.…”