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Synthesis and receptor binding of new thieno[2,3-d]-pyrimidines as selective ligands of 5-HT(3) receptors
- Source :
- Archiv der Pharmazie. 341(6)
- Publication Year :
- 2008
-
Abstract
- With the aim to develop new potent and selective ligands of 5-HT(3)-type serotonin receptors and to acquire more information on their structure-affinity relationships, new thieno[2,3-d]pyrimidine derivatives 32-39 were synthesized and their binding to 5-HT(3) versus 5-HT(4 )receptors was studied. Some of these new compounds exhibit good affinity for cortical 5-HT(3) receptors, but not for 5-HT(4) receptors. Among these derivatives, 6-ethyl-4-(4-methyl-1-piperazinyl)-2-(methylthio)thieno[2,3-d]pyrimidine 32 is the most potent ligand (K(i) = 67 nM); it behaves as a competitive antagonist of the 5-HT(3) receptor function in the guinea pig colon. Its binding interactions with 5-HT(3A )receptors were analysed by using receptor modelling and comparative docking.
- Subjects :
- Male
Models, Molecular
Serotonin 5-HT4 Receptor Antagonists
antagonist
5-HT3 receptors
receptor docking
thieno[2,3-d]pyrimidines
Stereochemistry
Colon
Guinea Pigs
Pharmaceutical Science
Class C GPCR
Thiophenes
In Vitro Techniques
Ligands
Binding, Competitive
Radioligand Assay
Structure-Activity Relationship
Isometric Contraction
Drug Discovery
Animals
Serotonin 5-HT3 Receptor Antagonists
Receptor
5-HT receptor
G protein-coupled receptor
thieno[2
Chemistry
3-d]pyrimidines
Brain
Muscle, Smooth
Ligand (biochemistry)
Combinatorial chemistry
Rats
Metabotropic receptor
Pyrimidines
Docking (molecular)
Competitive antagonist
Receptors, Serotonin, 5-HT4
Receptors, Serotonin, 5-HT3
Subjects
Details
- ISSN :
- 03656233
- Volume :
- 341
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Archiv der Pharmazie
- Accession number :
- edsair.doi.dedup.....1ee391fa28b66abf9f20781f54bccf37