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

María L López-Rodríguez; Ma José Morcillo; Esther Fernández; Bellinda Benhamú; Ignacio Tejada; David Ayala; Alma Viso; Mireia Olivella; Leonardo Pardo; Mercedes Delgado; Jorge Manzanares; José A Fuentes

doi:10.1016/s0960-894x(03)00160-4

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

Bioorg Med Chem Lett. 2003 Apr 17;13(8):1429-32. doi: 10.1016/s0960-894x(03)00160-4.

Authors

María L López-Rodríguez¹, Ma José Morcillo, Esther Fernández, Bellinda Benhamú, Ignacio Tejada, David Ayala, Alma Viso, Mireia Olivella, Leonardo Pardo, Mercedes Delgado, Jorge Manzanares, José A Fuentes

Affiliation

¹ Departamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense, E-28040 Madrid, Spain. mluzir@quim.ucm.es

PMID: 12668005
DOI: 10.1016/s0960-894x(03)00160-4

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Anti-Anxiety Agents / chemical synthesis
Anti-Anxiety Agents / pharmacology
Benzene Derivatives / chemistry
Benzene Derivatives / metabolism
Benzene Derivatives / pharmacology
Body Temperature / drug effects
Computer Simulation
Dose-Response Relationship, Drug
Drug Design
HeLa Cells
Humans
Mice
Models, Molecular
Piperazines / chemical synthesis*
Piperazines / chemistry
Piperazines / metabolism
Piperazines / pharmacology*
Pyrazines / chemical synthesis
Pyrazines / chemistry
Pyrazines / pharmacology
Quantitative Structure-Activity Relationship
Receptors, Adrenergic, alpha-1 / metabolism
Receptors, Serotonin, 5-HT1 / drug effects*
Receptors, Serotonin, 5-HT1 / metabolism
Serotonin Receptor Agonists / chemical synthesis*
Serotonin Receptor Agonists / chemistry
Serotonin Receptor Agonists / metabolism
Serotonin Receptor Agonists / pharmacology*
Synaptic Transmission / drug effects

Substances

2-((4-(naphth-1-yl)piperazin-1-yl)methyl)-1,4-dioxoperhydropyrrolo(1,2-a)pyrazine
Anti-Anxiety Agents
Benzene Derivatives
Piperazines
Pyrazines
Receptors, Adrenergic, alpha-1
Receptors, Serotonin, 5-HT1
Serotonin Receptor Agonists