Synthesis and in vitro biological evaluation of new P2X7R radioligands [11C]halo-GSK1482160 analogs.
Bioorg Med Chem Lett
; 29(12): 1476-1480, 2019 06 15.
Article
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| MEDLINE
| ID: mdl-31005444
ABSTRACT
The reference standards halo-GSK1482160 (F-, Br-, and I-) and their corresponding precursors desmethyl-halo-GSK1482160 (F-, Br-, and I-) were synthesized from (S)-1-methyl-5-oxopyrrolidine-2-carboxylic acid or (S)-5-oxopyrrolidine-2-carboxylic acid and 2-halo-3-(trifluoromethyl)benzylamine (F-, Br-, and I-) in one step with 45-93% yields. The target tracers [11C]halo-GSK1482160 (F-, Br-, and I-) were prepared from desmethyl-halo-GSK1482160 (F-, Br-, and I-) with [11C]CH3OTf under basic conditions (NaOH-Na2CO3, solid, w/w 12) through N-[11C]methylation and isolated by HPLC combined with SPE in 40-50% decay corrected radiochemical yield. The radiochemical purity wasâ¯>99%, and the molar activity (AM) at end of bombardment (EOB) was 370-740â¯GBq/µmol. The potency of halo-GSK1482160 (F-, Br-, and I-) in comparison with GSK1482160 (Cl-) was determined by a radioligand competitive binding assay using [11C]GSK1482160, and the binding affinity Ki values for halo-GSK1482160 (F-, Br-, and I-) and GSK1482160 (Cl-) are 54.2, 2.5, 1.9 and 3.1â¯nM, respectively.
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Banco de datos:
MEDLINE
Asunto principal:
Ensayo de Unión Radioligante
/
Radiofármacos
Límite:
Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article