Naphthyl piperazines with dual activity as 5-HT1D antagonists and 5-HT reuptake inhibitors

• Published in: Bioorganic & medicinal chemistry letters Vol. 17; no. 12; pp. 3344 - 3348
• Main Authors: Bueno, Ana B., Gilmore, Jeremy, Boot, John, Broadmore, Richard, Cooper, Jane, Findlay, Jeremy, Hayhurst, Lorna, Marcos, Alicia, Montero, Carlos, Mitchell, Stephen, Timms, Graham, Tomlinson, Rosemarie, Wallace, Louise, Walton, Leslie
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 15.06.2007
• Subjects: Animals; Antidepressive Agents - chemical synthesis; Antidepressive Agents - pharmacology; Biological and medical sciences; Dose-Response Relationship, Drug; Guinea Pigs; Kinetics; Medical sciences; Models, Chemical; Naphthalenes - chemistry; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Piperazines - chemical synthesis; Piperazines - pharmacology; Receptor, Serotonin, 5-HT1D - drug effects; Receptor, Serotonin, 5-HT1D - metabolism; Serotonin Antagonists - chemical synthesis; Serotonin Antagonists - pharmacology; Serotonin Uptake Inhibitors - chemical synthesis; Serotonin Uptake Inhibitors - pharmacology; Serotoninergic system; Stereoisomerism; Structure-Activity Relationship; Serotonin; Rodentia; Oral administration; Selectivity; Reuptake inhibitor; In vitro; Naphthalene derivatives; 5-HT1D serotonin receptor; In vivo; Vertebrata; Mammalia; Guinea pig; Structure activity relation; Animal; Cross reaction; Neurotransmitter; Antagonist; Piperazine derivatives; Chemical synthesis; Diastereomer; Serotonin reuptake inhibitor; 5-HT1D antagonist
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2007.03.101

SAR around a known molecule with dual 5-HT(1D) antagonist and 5-HT(transporter) inhibitory activity has led to the discovery of molecules with improved dual activity and reduced cross-reactivity toward other aminergic receptors (5-HT(1B), alpha(1), and D(2)).