Tricyclic heterocycles display diverse sensitivity to the A147T TSPO polymorphism.
Eur J Med Chem
; 207: 112725, 2020 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-32920427
ABSTRACT
The 18 kDa translocator protein (TSPO) is a target for the development of imaging agents to detect neuroinflammation. The clinical utility of second-generation TSPO ligands has been hindered by the presence of a polymorphism, rs6971, which causes a non-conservative substitution of alanine for threonine at amino acid residue 147 (TSPO A147T). Given the complex nature of TSPO binding, and the lack of non-discriminating high-affinity ligands at both wild type and A147T forms of TSPO, a series of novel TSPO ligands containing various heterocyclic scaffolds was developed to explore the pharmacophoric drivers of affinity loss at TSPO A147T. In general, N-benzyl-N-methyl-substituted amide ligands showed increased affinity at TSPO A147T, and a pyrazolopyrimidine acetamide containing this motif displayed low nanomolar binding affinities to both TSPO forms.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirazoles
/
Pirimidinas
/
Receptores de GABA
/
Radiofármacos
/
Compuestos Heterocíclicos
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
Eur J Med Chem
Año:
2020
Tipo del documento:
Article
País de afiliación:
Australia