Synthesis and preliminary biological evaluation of [11C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-D-leucinate for the fractalkine receptor (CX3CR1)

The reference standard methyl (2-amino-5-(benzylthio) thiazolo[4,5-d] pyrimidin-7-yl)-D-leucinate (5) and its precursor 2-amino-5-(benzylthio) thiazolo[4,5-d] pyrimidin-7-yl)-D-leucine (6) were synthesized from 6-amino-2-mercaptopyrimidin-4-ol and BnBr with overall chemical yield 7% in five steps and 4% in six steps, respectively. The target tracer [C-11] methyl (2-amino-5-(benzylthio) thiazolo[4,5-d] pyrimidin- 7-yl)-D-leucinate ([C-11] 5) was prepared from the acid precursor with [C-11] CH3OTf through O-[C-11] methylation and isolated by HPLC combined with SPE in 40-50% radiochemical yield, based on [C-11] CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370-1110 GBq/mu mol with a total synthesis time of similar to 40-min from EOB. The radioligand depletion experiment of [C-11] 5 did not display specific binding to CX(3)CR1, and the competitive binding assay of ligand 5 found much lower CX(3)CR1 binding affinity. (C) 2017 Elsevier Ltd. All rights reserved.