Synthesis and in vitro evaluation of new TRPV4 ligands and biodistribution study of an 11C-labeled radiotracer in rodents.
Bioorg Med Chem Lett
; 30(22): 127573, 2020 11 15.
Article
em En
| MEDLINE
| ID: mdl-32980513
ABSTRACT
Nine new compounds targeting the transient receptor potential vanilloid-4 (TRPV4) were synthesized and their biological activities toward TRPV4 were determined using freshly isolated mouse skin macrophages through live cell Ca2+ imaging assay. Three compounds 4b, 4c, and 4i exhibited higher percentages of in vitro activation of TRPV4 as 48.1%, 59.3% and 33.5%, which are comparable to 56.4% activation response of the reported TRPV4 agonist GSK1016790A (3). The compound 4i was chosen for 11C-radiosynthesis using its phenol precursor 4g to reacted with [11C]methyl iodide. The radiosynthesis was achieved with good radiochemical yield (16 ± 5%), high chemical and radiochemical purity (>95%), and high molar activity (16-21 GBq/µmol, decay corrected to the end of bombardment, EOB n ≥ 4). Furthermore, the initial ex vivo biodistribution study in rats showed that [11C]4i had higher uptake in kidney, liver and small intestine compared to other tissues with rapid washout.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos Radiofarmacêuticos
/
Canais de Cátion TRPV
Limite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos