Novel 1-aminoethyl-3-arylsulfonyl-1H-pyrrolo[2,3-b]pyridines are potent 5-HT(6) agonists.
A series of 1-aminoethyl-3-arylsulfonyl-1H-pyrrolo[2,3-b]pyridines 10a-z was prepared as novel 5-HT(6) ligands. The best compounds were high affinity, full agonists at 5-HT(6) receptors. Several agonists demonstrated good selectivity over other serotonergic and dopaminergic receptors. Acute administration of selective agonist 10e significantly increased extracellular GABA concentrations in rat frontal cortex. This compound also reduced adjunctive drinking behavior in the rat schedule-induced polydipsia assay, possibly predictive of efficacy in obsessive compulsive disorder and other anxiety related disorders.
Bernotas
Ronald C
RC
Chemical Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA. bernotr@wyeth.com
Lenicek
Steven
S
Antane
Schuyler
S
Cole
Derek C
DC
Harrison
Boyd L
BL
Robichaud
Albert J
AJ
Zhang
Guo Ming
GM
Smith
Deborah
D
Platt
Brian
B
Lin
Qian
Q
Li
Ping
P
Coupet
Joseph
J
Rosenzweig-Lipson
Sharon
S
Beyer
Chad E
CE
Schechter
Lee E
LE
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004327:Drinking Behavior / Q000187:drug effects*; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000378:metabolism
D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C097216:serotonin 6 receptor; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid