6533b822fe1ef96bd127d5d6
RESEARCH PRODUCT
Benzimidazoles as NMDA Glycine-Site Antagonists: Study on the Structural Requirements in 2-Position of the Ligand
Gerd DannhardtBeate K. Kohlsubject
chemistry.chemical_classificationBenzimidazoleChemistryStereochemistryLigandPharmaceutical ScienceGlycine receptor antagonistSulfonic acidchemistry.chemical_compoundAmideDrug DiscoveryGlycineMoietyCarboxylatedescription
A series of different substituted benzimidazole derivatives has been synthesized and evaluated for the ability to displace [3H]MDL-105,519 to rat cortical membranes. Two benzimidazole-2-carboxylic acids 9 b and 9 c, in this substitution pattern not yet described as glycine antagonists, showed IC50 values of 0.89 microM (9 b) and 38.0 microM (9 c). Replacement of the carboxylate function in 2-position by a sulfonic acid moiety appreciably increased solubility, but decreased the affinity giving evidence for the strong need of the carboxylate group within the ligand. Further structure-activity studies using benzimidazole-2-one derivatives with an acetic acid moiety adjacent to a ring nitrogen revealed new insights into the importance of amide functionalities within the heterocycle for the affinity of antagonist glycine-site ligands.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2000-05-01 | Archiv der Pharmazie |