1-Naphthylpiperazine derivatives as potential atypical antipsychotic agents.
The design and synthesis of a series of potential atypical antipsychotic agents based on the structure of 1-naphthylpiperazine are described. The incorporation of dopamine antagonist activity into the parent structure was achieved with heterocyclic surrogates for the catechol moiety of dopamine. Compound 4b from this series showed a biochemical profile that translated to behavioral activity in the rat predictive of an antipsychotic agent with a low propensity to cause extrapyramidal side effects in man.
Lowe
J A
JA
Central Research Division, Pfizer, Inc., Groton, Connecticut 06340.
Seeger
T F
TF
Nagel
A A
AA
Howard
H R
HR
Seymour
P A
PA
Heym
J H
JH
Ewing
F E
FE
Newman
M E
ME
Schmidt
A W
AW
Furman
J S
JS
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents; D001058:Apomorphine / Q000494:pharmacology; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D018492:Dopamine Antagonists; D006220:Haloperidol / Q000494:pharmacology; D007650:Ketanserin / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000378:metabolism
D000662:Amphetamines; D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D010879:Piperazines; D013764:Tetrahydronaphthalenes; C048241:1-(1-naphthyl)piperazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D006220:Haloperidol; D001058:Apomorphine; D011224:Prazosin