3-(Arylsulfonyl)-1-(azacyclyl)-1H-indoles are 5-HT(6) receptor modulators

Ronald C Bernotas; Schuyler Antane; Rajesh Shenoy; Van-Duc Le; Ping Chen; Boyd L Harrison; Albert J Robichaud; Guo Ming Zhang; Deborah Smith; Lee E Schechter

doi:10.1016/j.bmcl.2010.01.073

3-(Arylsulfonyl)-1-(azacyclyl)-1H-indoles are 5-HT(6) receptor modulators

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1657-60. doi: 10.1016/j.bmcl.2010.01.073. Epub 2010 Jan 21.

Authors

Ronald C Bernotas¹, Schuyler Antane, Rajesh Shenoy, Van-Duc Le, Ping Chen, Boyd L Harrison, Albert J Robichaud, Guo Ming Zhang, Deborah Smith, Lee E Schechter

Affiliation

¹ Chemical Sciences, Wyeth Pharmaceuticals, 500 Arcola Road, Collegeville, PA 19426, USA. bernotr@wyeth.com

PMID: 20138763
DOI: 10.1016/j.bmcl.2010.01.073

Abstract

Novel 3-(arylsulfonyl)-1-(azacyclyl)-1H-indoles 6 were synthesized as potential 5-HT(6) receptor ligands, based on constraining a basic side chain as either a piperidine or a pyrrolidine. Many of these compounds had good 5-HT(6) binding affinity with K(i) values <10nM. Depending on substitution, both agonists (e.g., 6o: EC(50)=60nM, E(max)=70%) and antagonists (6y: IC(50)=17 nM, I(max)=86%) were identified in a 5-HT(6) adenylyl cyclase assay.

MeSH terms

Humans
Indoles / chemical synthesis
Indoles / chemistry*
Indoles / pharmacology
Ligands
Receptors, Serotonin / chemistry*
Receptors, Serotonin / metabolism
Serotonin Antagonists / chemical synthesis
Serotonin Antagonists / chemistry*
Serotonin Antagonists / pharmacology
Serotonin Receptor Agonists / chemical synthesis
Serotonin Receptor Agonists / chemistry*
Serotonin Receptor Agonists / pharmacology
Structure-Activity Relationship
Sulfones / chemical synthesis
Sulfones / chemistry*
Sulfones / pharmacology

Substances

Indoles
Ligands
Receptors, Serotonin
Serotonin Antagonists
Serotonin Receptor Agonists
Sulfones
serotonin 6 receptor