Related Experiment Video
Updated: Aug 19, 2026

Stepwise Dosing Protocol for Increased Throughput in Label-Free Impedance-Based GPCR Assays
Published on: February 21, 2020
4-phenoxypiperidines: potent, conformationally restricted, non-imidazole histamine H3 antagonists
Curt A Dvorak1, Richard Apodaca, Ann J Barbier
1Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 3210 Merryfield Row, San Diego, California 92121, USA. cdvorak@prdus.jnj.com
Abstract:
Two new series of 4-(1-alkyl-piperidin-4-yloxy)-benzonitriles and 4-(1-isopropyl-piperidin-4-yloxy)-benzylamines have been prepared. In vitro activity was determined at the recombinant human H(3) receptor and several members of these new series were found to be potent H(3) antagonists. The present compounds contain a 4-phenoxypiperidine core, which behaves as a conformationally restricted version of the 3-amino-1-propanol moiety common to the many previously described non-imidazole histamine H(3) ligands. One selected member of the new series, 4-[4-(1-isopropyl-piperidin-4-yloxy)-benzyl]-morpholine (13g), was found to be a potent, highly selective H(3) receptor antagonist with in vivo efficacy in a rat EEG model of wakefulness at doses as low as 1 mg/kg sc.
Related Concept Videos
Acid Suppressive Drugs for Peptic Ulcer Disease: Histamine H2-Receptor Antagonists
Adrenergic Antagonists: Chemistry and Classification of ɑ-Receptor Blockers
Nonselective α-blockers: Nonselective α-blockers contain haloalkylamine or imidazoline moieties. Phenoxybenzamine, with a haloalkylamine...
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
Cholinergic Antagonists: Chemistry and Structure-Activity Relationship
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Basicity of Heterocyclic Aromatic Amines
