The influence of an ethylene spacer on the 5-HT(1A) and 5-HT(2A) receptor affinity of arylpiperazine derivatives of amides with N-acylated amino acids and 3-differently substituted pyrrolidine-2,5-diones.
A library of ethylene analogs of the previously described arylpiperazines with N-acylated amino acids was synthesized on SynPhase Lanterns and the library representatives were evaluated for their 5-HT(1A) and 5-HT(2A) receptor affinities. The obtained results were compared with those reported for compounds containing propylene and a butylene spacer and they revealed that 5-HT(1A) receptor affinity decreased proportionally with the length of the alkyl chain. Furthermore, the synthesized 3-cycloalkyl derivatives containing two methylene group spacers showed that the 3-position of pyrrolidine-2,5-dione preferred substituents of hydrophobic character.
Zajdel
Paweł
P
Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland. mfzajdel@cyf-kr.edu.pl
Subra
Gilles
G
Verdie
Pascal
P
Bojarski
Andrzej J
AJ
Duszyńska
Beata
B
Basista
Katarzyna
K
Obniska
Jolanta
J
Martinez
Jean
J
Pawłowski
Maciej
M
D000577:Amides / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D005030:Ethylenes / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D011485:Protein Binding; D011759:Pyrrolidines / Q000737:chemistry; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship
D000577:Amides; D000596:Amino Acids; D005030:Ethylenes; D010879:Piperazines; D011759:Pyrrolidines; D044402:Receptor, Serotonin, 5-HT2A; D054852:Small Molecule Libraries; D044282:Receptor, Serotonin, 5-HT1A; D000077489:Piperazine; C032519:pyrrolidine