A structure-affinity relationship study on derivatives of N-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide, a high-affinity and selective D(4) receptor ligand.
N-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (1), a high-affinity and selective dopamine D(4) receptor ligand, was chosen as a lead, and structural modifications were done on its amide bond and on its alkyl chain linking the benzamide moiety to the piperazine ring and by preparing some semirigid analogues. The binding profile at dopamine D(4) and dopamine D(2), serotonin 5-HT(1A), and adrenergic alpha(1) receptors of 16 new compounds was determined. From the results emerged that the modification of the amide bond and the elongation of the intermediate alkyl chain caused a decrease in dopamine D(4) receptor affinity. All prepared semirigid analogues displayed D(4) receptor affinity values in the same range of the opened counterparts.
Perrone
R
R
Dipartimento Farmaco-Chimico, Universitá di Bari, via Orabona, 4, 70126 Bari, Italy. perrone@farmchim.uniba.it
Berardi
F
F
Colabufo
N A
NA
Leopoldo
M
M
Tortorella
V
V
D000818:Animals; D001549:Benzamides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015259:Dopamine Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050638:Receptors, Dopamine D4; D011985:Receptors, Serotonin / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
D001549:Benzamides; C493599:DRD4 protein, human; D015259:Dopamine Agents; C493601:Drd4 protein, rat; D008024:Ligands; C115935:N-(2-(4-(4-chlorophenyl)piperazin-1-yl)ethyl)-3-methoxybenzamide; D010879:Piperazines; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D011994:Recombinant Proteins; D050638:Receptors, Dopamine D4