Synthesis and pharmacological characterization of the selective GluK1 radioligand (S)-2-amino-3-(6-[3H]-2,4-dioxo-3,4-dihydrothieno[3,2-d]pyrimidin-1(2H)-yl)propanoic acid ([3H]-NF608)

Anna Alcaide,Stine Møllerud,Laura Marconi,Paola Conti,Lennart Bunch,Ales Marek,Birgitte Nielsen,Isabell Haym,Mikael Jensen,Darryl S Pickering

doi:10.1039/c6md00339g

Abstract

Expedite synthesis of [3H]NF608 – a new subtype selective GluK1 radioligand.

Highlights

In conclusion we have reported a short and efficient method for the radiosynthesis of the selective GluK1 radioligand [3H]NF608
The radioligand was characterized in in vitro binding assays at cloned homomeric GluK1 receptors and binding affinities (Ki) of a series of standard GluK1 ligands were shown to be in line with previously reported affinities obtained by use of already reported radioligands
Reactions were monitored by analytical thin-layer chromatography (TLC, Merck silica gel 60 F254 aluminum sheets), analytical HPLC or UPLC

Summary

Introduction

Results and discussion SynthesisFirstly, we pursued a direct bromination of commercially available UBP310 to obtain the dibromothiophene precursor previously reported for the synthesis of [3H]-UBP310 (Scheme S1, ESI‡).[3]. The solvent of the reaction mixture was co-evaporated with toluene (3 × 20 mL) to get a white solid that was divided in 6 portions and each one was dissolved in DMSO–MeCN (15 : 1, 1 mL) and purified by 6 consecutive preparative HPLC purifications (Rt: 19.53 min; flow: 10 mL min−1; A–B 1 : 0 to 25 : 75 (25 min); A–B 25 : 75 (5 min); preferably λ = 254 nm, since DMSO does not absorb) to afford the desired compound 3 as a white solid (206 mg, 11%), recovering the starting material thienoij3,2-d]pyrimidin-4IJ3H)-one (Rt: 14.29 min; 109 mg, 11%).

Results

Conclusion