Design and synthesis of S-(-)-2-[[4-(napht-1-yl)piperazin-1-yl]methyl]-1,4-dioxoperhydropyrrolo[1,2-a]pyrazine (CSP-2503) using computational simulation. A 5-HT1A receptor agonist.
Based on a computational model for 5-HT(1A)R-ligand interaction and QSAR studies, we have designed and synthesized a new series of arylpiperazines 2-8 which exhibit high 5-HT(1A)R affinity and selectivity over alpha(1)-adrenergic receptors. Among them, compound CSP-2503 (4) has been pharmacologically characterized as a 5-HT(1A)R agonist at somatodendritic and postsynaptic sites, endowed with anxiolytic properties.
López-Rodríguez
María L
ML
Departamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense, E-28040 Madrid, Spain. mluzir@quim.ucm.es
Morcillo
Ma José
MJ
Fernández
Esther
E
Benhamú
Bellinda
B
Tejada
Ignacio
I
Ayala
David
D
Viso
Alma
A
Olivella
Mireia
M
Pardo
Leonardo
L
Delgado
Mercedes
M
Manzanares
Jorge
J
Fuentes
José A
JA
D000595:Amino Acid Sequence; D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001555:Benzene Derivatives / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1 / Q000187:drug effects* / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects
C479225:2-((4-(naphth-1-yl)piperazin-1-yl)methyl)-1,4-dioxoperhydropyrrolo(1,2-a)pyrazine; D014151:Anti-Anxiety Agents; D001555:Benzene Derivatives; D010879:Piperazines; D011719:Pyrazines; D018340:Receptors, Adrenergic, alpha-1; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists