Related Experiment Video
Updated: Jul 5, 2026

Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors
Published on: June 7, 2016
Development of potent and selective small-molecule human Urotensin-II antagonists
John J McAtee1, Jason W Dodson, Sarah E Dowdell
1Department of Medicinal Chemistry, Cardiovascular and Urogenital Center of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA. jeff.j.mcatee@gsk.com
Abstract:
This work describes the development of potent and selective human Urotensin-II receptor antagonists starting from lead compound 1, (3,4-dichlorophenyl)methyl{2-oxo-2-[3-phenyl-2-(1-pyrrolidinylmethyl)-1-piperidinyl]ethyl}amine. Several problems relating to oral bioavailability, cytochrome P450 inhibition, and off-target activity at the kappa opioid receptor and cardiac sodium channel were addressed during lead development. hUT binding affinity relative to compound 1 was improved by more than 40-fold in some analogs, and a structural modification was identified which significantly attenuated both off-target activities.
Related Concept Videos
Antihypertensive Drugs: Direct Renin Inhibitors
Antihypertensive Drugs: Angiotensin II Receptor Blockers
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
Adrenergic Antagonists: Pharmacological Actions of ɑ-Receptor Blockers
α1-blockers: These drugs inhibit α1-adrenoceptors on smooth muscle cells, resulting in vasodilation. This vasodilation lowers blood pressure, making α1-blockers valuable in treating hypertension. Additionally, α1-blockers effectively address urinary obstruction...
Adrenergic Antagonists: Chemistry and Classification of ɑ-Receptor Blockers
Nonselective α-blockers: Nonselective α-blockers contain haloalkylamine or imidazoline moieties. Phenoxybenzamine, with a haloalkylamine...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

