Identification of a novel series of 3-piperidinyl-5-sulfonylindazoles as potent 5-HT6 ligands.
Cognitive dysfunction is a characteristic of various forms of dementia such as Alzheimer's disease (AD) and a core feature of schizophrenia. As part of our continuing efforts to develop agents for cognitive enhancement, we have been focused on the 5-HT(6) receptor-one of the emerging therapeutic targets in this area. Herein, we report the identification of a novel series of 3-piperidinyl-5-sulfonylindazole derivatives as potent 5-HT(6) antagonists. The synthesis and SAR of this class of compounds are reported.
Liu
Kevin G
KG
Chemical Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, USA. liuk1@wyeth.com
Lo
Jennifer R
JR
Comery
Thomas A
TA
Zhang
Guo Ming
GM
Zhang
Jean Y
JY
Kowal
Dianne M
DM
Smith
Deborah L
DL
Di
Li
L
Kerns
Edward H
EH
Schechter
Lee E
LE
Robichaud
Albert J
AJ
D003072:Cognition Disorders / Q000188:drug therapy; D003704:Dementia / Q000188:drug therapy; D006801:Humans; D007191:Indazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008024:Ligands; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D013441:Sulfinic Acids / Q000138:chemical synthesis / Q000494:pharmacology
D007191:Indazoles; D008024:Ligands; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013441:Sulfinic Acids; C097216:serotonin 6 receptor