Novel selective and potent 5-HT reuptake inhibitors with 5-HT1D antagonist activity: chemistry and pharmacological evaluation of a series of thienopyran derivatives

• Published in: Bioorganic & medicinal chemistry Vol. 12; no. 20; pp. 5277 - 5295
• Main Authors: Torrado, Alicia, Lamas, Carlos, Agejas, Javier, Jiménez, Alma, Dı́az, Nuria, Gilmore, Jeremy, Boot, John, Findlay, Jeremy, Hayhurst, Lorna, Wallace, Louise, Broadmore, Richard, Tomlinson, Rosemarie
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Science 15.10.2004
• Subjects: Animals; Biological and medical sciences; Humans; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Pyrans - chemical synthesis; Pyrans - chemistry; Pyrans - pharmacology; Rats; Serotonin 5-HT1 Receptor Antagonists; Serotonin Antagonists - chemical synthesis; Serotonin Antagonists - chemistry; Serotonin Antagonists - pharmacology; Serotonin Uptake Inhibitors - chemical synthesis; Serotonin Uptake Inhibitors - chemistry; Serotonin Uptake Inhibitors - pharmacology; Serotoninergic system; Human; Oxygen sulfur heterocycle; Rat; Serotonin; Rodentia; Selectivity; Reuptake inhibitor; Condensed benzenic compound; In vitro; Naphthalene derivatives; Uptake; 5-HT1D serotonin receptor; Vertebrata; Mammalia; Structure activity relation; Membrane transport; Animal; Bicyclic compound; Affinity; Antagonist; Inhibition; Piperazine derivatives; Chemical synthesis; Carrier protein
• ISSN: 0968-0896
• DOI: 10.1016/j.bmc.2004.07.059

A series of compounds combining the naphthylpiperazine and thienopyran scaffolds has been prepared and evaluated for 5-HT reuptake inhibition with 5-HT1D antagonist activity. The design of these compounds has been based on the 'overlapping type' strategy where two pharmacophores are linked in a single molecule. The resultant dual pharmacological profile has the potential to deliver a more efficient treatment for depression.