Unknown

Dataset Information

0

N-Hydroxypyrazolyl glycine derivatives as selective N-methyl-D-aspartic acid receptor ligands.


ABSTRACT: A series of analogues based on N-hydroxypyrazole as a bioisostere for the distal carboxylate group of aspartate have been designed, synthesized, and pharmacologically characterized. Affinity studies on the major glutamate receptor subgroups show that these 4-substituted N-hydroxypyrazol-5-yl glycine (NHP5G) derivatives are selectively recognized by N-methyl- d-aspartic acid (NMDA) receptors and that the ( R)-enantiomers are preferred. Moreover, several of the compounds are able to discriminate between individual subtypes among the NMDA receptors, providing new pharmacological tools. For example, 4-propyl NHP5G is an antagonist at the NR1/NR2A subtype but an agonist at the NR1/NR2D subtype. Molecular docking studies indicate that the substituent protrudes into a region that may be further exploited to improve subtype selectivity, thereby opening up a design strategy for ligands which can differentiate individual NMDA receptor subtypes.

SUBMITTER: Clausen RP 

PROVIDER: S-EPMC4850074 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications


A series of analogues based on N-hydroxypyrazole as a bioisostere for the distal carboxylate group of aspartate have been designed, synthesized, and pharmacologically characterized. Affinity studies on the major glutamate receptor subgroups show that these 4-substituted N-hydroxypyrazol-5-yl glycine (NHP5G) derivatives are selectively recognized by N-methyl- d-aspartic acid (NMDA) receptors and that the ( R)-enantiomers are preferred. Moreover, several of the compounds are able to discriminate b  ...[more]

Similar Datasets

| S-EPMC3885094 | biostudies-literature
| S-EPMC3689883 | biostudies-literature
| S-EPMC3322860 | biostudies-literature
| S-EPMC3089538 | biostudies-literature
| S-EPMC7267813 | biostudies-literature
| S-EPMC2096654 | biostudies-literature
| S-EPMC10108392 | biostudies-literature
| S-EPMC8622018 | biostudies-literature
| S-EPMC3684822 | biostudies-literature
| S-EPMC7013949 | biostudies-literature