3-(4-Piperidinyl)- and 3-(8-aza-bicyclo[3.2.1]oct-3-yl)-2-phenyl-1H-indoles as bioavailable h5-HT2A antagonists.
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.
Crawforth
J
J
Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Harlow, Essex, UK. james_crawforth@merck.com
Goodacre
S
S
Maxey
R
R
Bourrain
S
S
Patel
S
S
Marwood
R
R
O'Connor
D
D
Herbert
R
R
Hutson
P
P
Rowley
M
M
D000284:Administration, Oral; D000818:Animals; D001667:Binding, Competitive; D001682:Biological Availability; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D008024:Ligands; D010880:Piperidines / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
D019086:Bridged Bicyclo Compounds, Heterocyclic; D007211:Indoles; D008024:Ligands; D010880:Piperidines; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists