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Arylpiperazinylalkyl derivatives of 8-amino-1,3-dimethylpurine-2,6-dione as novel multitarget 5-HT/D receptor agents with potential antipsychotic activity
- Source :
- Journal of enzyme inhibition and medicinal chemistry. 31(6)
- Publication Year :
- 2015
-
Abstract
- A series of new 7-arylpiperazinylalkyl-1,3-dimethyl-purine-2,6-dione derivatives with diversified 8-amino substituent in 8 position was synthesized and their 5-HT1A, 5-HT2A, 5-HT6, 5-HT7, and D2 receptor affinities were determined. The binding study allowed identifying some potent 5-HT1A/5-HT2A/5-HT7/D2 ligands. The most interesting because of their multireceptor profile were 8-piperidine (30–35) and 8-dipropylamine (45–47) analogs with four and five carbon aliphatic linkers. The selected compounds 24, 31, 34, 39, 41, 43, 45, and 46 in the functional in vitro evaluation for all targeted receptors showed significant partial D2 agonist, partial 5-HT1A agonist, and 5-HT2A antagonist properties. The advantageous in vitro affinity of compound 34 for 5-HT1A and D2 receptors has been explained by means of molecular modeling, taking into consideration its partial agonist activity towards the latter one. In behavioral studies, compounds 32 and 34 revealed antipsychotic-like properties, significantly decreasing d-amphetamine-induced hyperactivity in mice.
- Subjects :
- 0301 basic medicine
Pharmacology
Agonist
Molecular model
medicine.drug_class
Proton Magnetic Resonance Spectroscopy
Antagonist
Substituent
General Medicine
Combinatorial chemistry
Partial agonist
Piperazines
03 medical and health sciences
chemistry.chemical_compound
030104 developmental biology
chemistry
Purines
Dopamine receptor D2
Receptors, Serotonin
Drug Discovery
medicine
Receptor
5-HT receptor
Antipsychotic Agents
Chromatography, Liquid
Subjects
Details
- ISSN :
- 14756374
- Volume :
- 31
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of enzyme inhibition and medicinal chemistry
- Accession number :
- edsair.doi.dedup.....5bd421c0ff131f160c225e33f1e036f9