Potent and selective oxindole-based vasopressin 1b receptor antagonists with improved pharmacokinetic properties
Thorsten Oost1, Gisela Backfisch, Swati Bhowmik
1Abbott, Neuroscience Discovery, Ludwigshafen, Germany.
Abstract:
Herein we report the discovery of a novel series of vasopressin 1b (V1b) receptor antagonists, starting from potent but metabolically labile oxindole SSR149415. Masking the proline N,N-dimethyl amide moiety as an oxazole and attaching a benzylic amine moiety to the northern phenyl ring resulted in potent and selective V1b receptor antagonists with improved metabolic stability and improved pharmacokinetic properties in rat. Compound 18c was found to be efficacious in a rat model of anti-depressant activity.
Related Concept Videos
Antihypertensive Drugs: Vasodilators
Drug-Receptor Interaction: Antagonist
Antagonists can be classified as competitive or noncompetitive based on their...
Indirect-Acting Cholinergic Agonists: Pharmacokinetics
Reversible agents containing quaternary amines, such as neostigmine and edrophonium, are not easily absorbed orally because they are...
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 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 β-Receptor Blockers


