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

J Crawforth; S Goodacre; R Maxey; S Bourrain; S Patel; R Marwood; D O'Connor; R Herbert; P Hutson; M Rowley

doi:10.1016/s0960-894x(00)00559-x

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

Bioorg Med Chem Lett. 2000 Dec 18;10(24):2701-3. doi: 10.1016/s0960-894x(00)00559-x.

Authors

J Crawforth¹, S Goodacre, R Maxey, S Bourrain, S Patel, R Marwood, D O'Connor, R Herbert, P Hutson, M Rowley

Affiliation

¹ Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Harlow, Essex, UK. james_crawforth@merck.com

PMID: 11133072
DOI: 10.1016/s0960-894x(00)00559-x

Abstract

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.

MeSH terms

Administration, Oral
Animals
Binding, Competitive
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
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
Structure-Activity Relationship

Substances

Bridged Bicyclo Compounds, Heterocyclic
Indoles
Ligands
Piperidines
Receptors, Dopamine D2
Receptors, Serotonin
Serotonin Antagonists