3-(4-Piperidinyl)- and 3-(8-aza-bicyclo[3.2.1]oct-3-yl)-2-phenyl-1h-indoles as bioavailable h5-HT2A antagonists

• Published in: Bioorganic & medicinal chemistry letters Vol. 10; no. 24; pp. 2701 - 2703
• Main Authors: CRAWFORTH, James, GOODACRE, Simon, MAXEY, Robert, BOURRAIN, Sylvie, PATEL, Smita, MARWOOD, Rosemarie, O'CONNOR, Desmond, HERBERT, Richard, HUTSON, Peter, ROWLEY, Michael
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 18-12-2000
• Subjects: Administration, Oral; Animals; Binding, Competitive; Biological and medical sciences; Biological Availability; Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis; Bridged Bicyclo Compounds, Heterocyclic - pharmacokinetics; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Humans; Indoles - chemical synthesis; Indoles - pharmacokinetics; Indoles - pharmacology; Ligands; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Piperidines - chemical synthesis; Piperidines - pharmacokinetics; Piperidines - pharmacology; Rats; Receptors, Dopamine D2 - metabolism; Receptors, Serotonin - metabolism; Serotonin Antagonists - chemical synthesis; Serotonin Antagonists - pharmacokinetics; Serotonin Antagonists - pharmacology; Serotoninergic system; Structure-Activity Relationship; Rat; Nitrogen heterocycle; Rodentia; Oral administration; Selectivity; Bioavailability; In vitro; 5-HT2 Serotonine receptor; Vertebrata; Mammalia; Structure activity relation; Animal; Piperidine derivatives; Bicyclic compound; Aromatic compound; Antagonist; Indole derivatives; Pharmacokinetics; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(00)00559-X

A series of 3-(4-piperidinyl)- and 3-(8-aza-bicyclo[3.2.1]oct-3-yl)-2-phenyl-1H-indoles have been prepared and evaluated as ligands for the h5-HT2A receptor. 3-(8-Phenethyl-8-aza-bicyclo[3.2.1]oct-3-yl)-2-phenyl-1H-indole is a high-affinity (1.2nM), selective (>800 fold over h5-HT2C and hD2 receptors) antagonist at the h5-HT2A receptor with oral bioavailability in rats.