Format:
Online-Ressource
ISSN:
1860-7187
Content:
Abstract: Previous structure–activity relationship studies in the search for a potent, noncompetitive α‐amino‐3‐(3‐hydroxy‐5‐methyl‐4‐isoxazolyl) propionic acid (AMPA) receptor antagonist led to 2,3‐dimethyl‐6‐phenyl‐12H‐[1,3]dioxolo[4,5‐h]imidazo[1,2‐c][2,3]benzodiazepine (ZK 187638). However, the first synthesis had some drawbacks regarding reagents, processes, and overall yield, which furthermore decreased when the synthesis was scaled up. Therefore, we now report a new synthetic route for this compound which requires fewer steps and is suited for large‐scale production. This compound significantly relieved the symptoms of neuromuscular deficit in mnd mice, a model of neuronal ceroid lipofuscinosis with motor neuron dysfunction. After oral administration, the concentrations of the compound in the brain and spinal cord were about threefold higher than those in the plasma. In summary, this novel AMPA antagonist is accessible through an optimized synthetic route, has good neurobehavioral activity, oral bioavailability, and favorable brain penetration. This opens new possibilities for the treatment of devastating neurological diseases that are mediated by the AMPA receptor.
In:
volume:1
In:
number:10
In:
year:2006
In:
pages:1142-1148
In:
extent:7
In:
ChemMedChem, Weinheim : Wiley-VCH, [2006]-, 1, Heft 10 (2006), 1142-1148 (gesamt 7), 1860-7187
Language:
English
DOI:
10.1002/cmdc.200600144
URN:
urn:nbn:de:101:1-2023082504405440922258
URL:
https://doi.org/10.1002/cmdc.200600144
URL:
https://nbn-resolving.org/urn:nbn:de:101:1-2023082504405440922258
URL:
https://d-nb.info/1300085177/34
URL:
https://doi.org/10.1002/cmdc.200600144
Bookmarklink