Tetrahydrocarbazole-based serotonin reuptake inhibitor/dopamine D2 partial agonists for the potential treatment of schizophrenia.
A 5-fluoro-tetrahydrocarbazole serotonin reuptake inhibitor (SRI) building block was combined with a variety of linkers and dopamine D2 receptor ligands in an attempt to identify potent D2 partial agonist/SRI molecules for treatment of schizophrenia. This approach has the potential to treat a broader range of symptoms compared to existing therapies. Selected compounds in this series demonstrate high affinity for both targets and D2 partial agonism in cell-based and in vivo assays.
Rotella
David P
DP
Chemical Sciences, Wyeth Research, CN 8000 Princeton, NJ 08543, United States. rotelld@wyeth.com
McFarlane
Geraldine R
GR
Greenfield
Alexander
A
Grosanu
Cristina
C
Robichaud
Albert J
AJ
Denny
Rajiah Aldrin
RA
Feenstra
Rolf W
RW
Núñez-García
Sara
S
Reinders
Jan-Hendrik
JH
Neut
Martina van der
Mv
McCreary
Andrew
A
Kruse
Chris G
CG
Sullivan
Kelly
K
Pruthi
Farhana
F
Lai
Margaret
M
Zhang
Jean
J
Kowal
Dianne M
DM
Carrick
Tikva
T
Grauer
Steven M
SM
Navarra
Rachel L
RL
Graf
Radka
R
Brennan
Julie
J
Marquis
Karen L
KL
Pausch
Mark H
MH
D000818:Animals; D002227:Carbazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy*; D058829:Serotonin 5-HT1 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D002227:Carbazoles; D018491:Dopamine Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017448:Receptors, Dopamine D2; D058829:Serotonin 5-HT1 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors