5-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-phenyl-2,3,6,7-tetrahydro-1,4-thiazepines as compounds with high affinity at the benzodiazepine binding site on GABA(A) receptors

C Grunwald; C Kronbach; U Egerland; R Schindler; R Dieckmann; K Heinecke; N Höfgen; K Unverferth

doi:10.1002/chin.201125210

5-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-phenyl-2,3,6,7-tetrahydro-1,4-thiazepines as compounds with high affinity at the benzodiazepine binding site on GABA(A) receptors

Pharmazie. 2011 Feb;66(2):98-104. doi: 10.1002/chin.201125210.

Authors

C Grunwald¹, C Kronbach, U Egerland, R Schindler, R Dieckmann, K Heinecke, N Höfgen, K Unverferth

Affiliation

¹ Biocrea GmbH, Radebeul, Germany. [email protected]

PMID: 21434570
DOI: 10.1002/chin.201125210

Abstract

A series of thiazepines has been studied as new ligands for the benzodiazepine binding site of the GABAA receptor. Compounds with high affinity and weak selectivity regarding alpha beta3gamma2, alpha2beta3gamma2, alpha3beta3gamma2, and alpha5beta3gamma2 subtypes were found. The pharmacophore is discussed based on experimental and theoretical results. The thiazepine sulfur atom was found to be able to act as hydrogen bond acceptor.

Publication types

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

MeSH terms

Chromatography, High Pressure Liquid
GABA Agents / chemical synthesis*
GABA Agents / pharmacology*
HEK293 Cells
Humans
Indicators and Reagents
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Conformation
Pyrans / chemistry*
Receptors, GABA-A / drug effects*
Recombinant Proteins / chemistry
Reference Standards
Spectrophotometry, Ultraviolet
Stereoisomerism
Structure-Activity Relationship
Thiazepines / chemistry*

Substances

5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-phenyl-2,3,6,7-tetrahydro-1,4-thiazepine
GABA Agents
Indicators and Reagents
Pyrans
Receptors, GABA-A
Recombinant Proteins
Thiazepines