3-(Arylsulfonyl)-1-(azacyclyl)-1H-indoles are 5-HT(6) receptor modulators.
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.
Chemical Sciences, Wyeth Pharmaceuticals, 500 Arcola Road, Collegeville, PA 19426, USA. bernotr@wyeth.com
Ronald C
RC
Bernotas
Schuyler
S
Antane
Rajesh
R
Shenoy
Van-Duc
VD
Le
Ping
P
Chen
Boyd L
BL
Harrison
Albert J
AJ
Robichaud
Guo Ming
GM
Zhang
Deborah
D
Smith
Lee E
LE
Schechter
D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D011985:Receptors, Serotonin / Q000737:chemistry* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D007211:Indoles; D008024:Ligands; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013450:Sulfones; C097216:serotonin 6 receptor