Journal of Medicinal Chemistry p. 618 - 624 (1988)
Update date:2022-07-30
Topics:
New, James S.
Yevich, Joseph P.
Temple, Davis L.
New, Kimberly B.
Gross, Sharon M.
et al.
A series of 3-substituted 2-pyridinyl-1-piperazine derivaties have been appended to cyclic imide groups and evaluated for their potential antipsochotic activity.The dopamine receptor affinities of these target molecules, as well as their ability to block apomorphine-induced stereotypy or reverse neuroleptic-induced catalepsy, was dependent on the lipophilic and electronic characteristics of the substituent situated on the pyridine ring.Groups with +? and -? values were most consistent with the desired biological profile of the target molecules, the cyano moiety being the optimum choice.Evaluation of compound 12 in a monkey model of amphetamine psychosis, and the regional selectivity it expresses for the A10 dopaminergic cell bodies in electrophysiological experiments, suggest this compound would be an atypical antipsychotic agent with few side effects.
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