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N ‐(4‐(4‐(2‐Halogenophenyl)piperazin‐1‐yl)butyl) Substituted Cinnamoyl Amide Derivatives as Dopamine D 2 and D 3 Receptor Ligands
Author(s) -
Saur Oliver,
Hackling Anneke E.,
Perachon Sylvie,
Schwartz JeanCharles,
Sokoloff Pierre,
Stark Holger
Publication year - 2007
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200600196
Subject(s) - amide , chemistry , selectivity , agonist , affinities , stereochemistry , receptor , biochemistry , catalysis
A series of eight substituted N ‐(4‐(4‐(2‐halogenophenyl)piperazin‐1‐yl)butyl)‐3‐phenylacryl amide derivatives have been synthesized and screened for binding affinities at dopamine hD 2 and hD 3 receptors. All compounds have shown high to remarkable receptor affinities and some have led to distinct selectivity for D 3 receptors. Highest D 3 ‐receptor affinity has been observed for 3‐(4‐aminophenyl)‐ N ‐(4‐(4‐(2‐fluorophenyl)piperazin‐1‐yl)butyl)acryl amide (hD 3 K i 0.9 nM; hD 2 K i 17.4 nM). Selectivity ratio has been best for 3‐(4‐chlorophenyl)‐ N ‐(4‐(4‐(2‐fluorophenyl)piperazin‐1‐yl)butyl)acryl amide with a 56‐fold preference for hD 3 versus hD 2 . A functional activity test has been performed by a mitogenesis test for N ‐(4‐(4‐(2‐fluorophenyl)piperazin‐1‐yl)butyl)‐3,3‐diphenylacryl amide, which, surprisingly, has shown full agonist properties.