Thieno (2,3-b) pyridinones as Antagonists on the Glycine Site of the N-methyl-D-asparatate Receptor-Binding Studies, Molecular Modeling and Structure-Activity-Relationships
- Author(s)
- H -P Buchstaller, C D Siebert, R.H. Lyssy, Gerhard Ecker, M Krug, Michael Berger, Rudolf Gottschlich, Christian Noe
- Abstract
Within the frame of the synthesis of glycine antagonists, a series of novel thieno[2,3-b]pyridinones with substituted phenyl residues in position 5 were synthesised to investigate the importance of the torsion angle between the pyridinone skeleton and the phenyl ring for binding affinity. The parent compound, 4-hydroxy-5-phenylthieno[2,3-b]pyridine-6(7H)-one, and its thienyl analogue, exhibited highest potencies, whereas compounds with ortho- substituted aryl moleties in position 5 showed decreased activities. This seems to be due to unfavourable steric interactions and increased torsion angles between the thieno[2,3-b]pyridinone system and the aryl substituent in position 5. Further evidence is drawn by QSAR studies, which showed an inverse relationship between the size of the ortho-substituent and the binding affinity.
- Organisation(s)
- External organisation(s)
- Merck KGaA, Johann Wolfgang Goethe-Universität Frankfurt am Main
- Journal
- Scientia Pharmaceutica
- Pages
- 3-14
- No. of pages
- 12
- ISSN
- 0036-8709
- Publication date
- 2000
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 3012 Pharmacy, Pharmacology, Toxicology
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/75d36783-94ac-45d2-baeb-815c60ce4e0f