Identification of a series of benzoxazoles as potent 5-HT6 ligands.
As part of our continuing efforts to identify therapeutics for CNS diseases such as schizophrenia and Alzheimer's disease (AD), we have been focused on the 5-HT(6) receptor in order to identify potent and selective ligands as a potential treatment for cognitive dysfunction. Herein we report the identification of a novel series of benzoxazole derivatives as potent 5-HT(6) ligands. The synthesis and detailed SAR of this class of compounds are reported. The compounds have been shown to be full antagonists in a cyclic AMP functional assay.
Liu
Kevin G
KG
Chemical & Screening 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
D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003072:Cognition Disorders / Q000188:drug therapy*; D020650:Combinatorial Chemistry Techniques; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011985:Receptors, Serotonin / Q000187:drug effects*; D018490:Serotonin Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001583:Benzoxazoles; D008024:Ligands; D011985:Receptors, Serotonin; D018490:Serotonin Agents; C097216:serotonin 6 receptor; D000242:Cyclic AMP