Gao, MingzhangWang, MinGlick-Wilson, Barbara E.Meyer, Jill A.Peters, Jonathan S.Territo, Paul R.Green, Mark A.Hutchins, Gary D.Zarrinmayeh, HamidehZheng, Qi-Huang2018-10-262018-10-262018-05Gao, M., Wang, M., Glick-Wilson, B. E., Meyer, J. A., Peters, J. S., Territo, P. R., … Zheng, Q.-H. (2018). Synthesis and preliminary biological evaluation of a novel P2X7R radioligand [18F]IUR-1601. Bioorganic & Medicinal Chemistry Letters, 28(9), 1603–1609. https://doi.org/10.1016/j.bmcl.2018.03.044https://hdl.handle.net/1805/17653The reference standard IUR-1601 ((S)-N-(2-chloro-3-(trifluoromethyl)benzyl)-1-(2-fluoroethyl)-5-oxopyrrolidine-2-carboxamide) was synthesized from tert-butyl (S)-5-oxopyrrolidine-2-carboxylate, fluoroethylbromide, and 2-chloro-3-(trifluoromethyl)benzylamine with overall chemical yield 12% in three steps. The target tracer [18F]IUR-1601 ((S)-N-(2-chloro-3-(trifluoromethyl)benzyl)-1-(2-[18F]fluoroethyl)-5-oxopyrrolidine-2-carboxamide) was synthesized from desmethyl-GSK1482160 with 2-[18F]fluoroethyl tosylate, prepared from 1,2-ethylene glycol-bis-tosylate and K[18F]F/Kryptofix2.2.2, in two steps and isolated by HPLC combined with SPE in 1–3% decay corrected radiochemical yield. The radiochemical purity was >99%, and the molar activity at end of bombardment (EOB) was 74–370 GBq/μmol. The potency of IUR-1601 in comparison with GSK1482160 was determined by a radioligand competitive binding assay using [11C]GSK1482160, and the binding affinity Ki values for IUR-1601 and GSK1482160 are 4.31 and 5.14 nM, respectively.enPublisher Policy[18F]IUR-1601((S)-N-(2-chloro-3-(trifluoromethyl)benzyl)-1-(2-[18F]fluoroethyl)-5-oxopyrrolidine-2-carboxamide)purinergic P2X7 receptor (P2X7R)Article