Synthesis and preliminary biological evaluation of a novel P2X7R radioligand [18F]IUR-1601

Mingzhang Gao, Min Wang, Barbara E. Glick-Wilson, Jill A. Meyer, Jonathan S. Peters, Paul Territo, Mark Green, Gary Hutchins, Hamideh Zarrinmayeh, Qi-Huang Zheng

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The 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.

Original languageEnglish (US)
Pages (from-to)1603-1609
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume28
Issue number9
DOIs
StatePublished - May 15 2018

Fingerprint

Competitive Binding
Ethylene Glycol
Assays
High Pressure Liquid Chromatography
N-(2-chloro-3-(trifluoromethyl)benzyl)-N-methyl-5-oxopyrrolidine-2-carboxamide
benzylamine
fluoroethyl tosylate

Keywords

  • Competitive binding assay
  • Positron emission tomography (PET)
  • Purinergic P2X7 receptor (P2X7R)
  • Radiosynthesis
  • [F]IUR-1601 ((S)-N-(2-chloro-3-(trifluoromethyl)benzyl)-1-(2-[F]fluoroethyl)-5-oxopyrrolidine-2-carboxamide)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Synthesis and preliminary biological evaluation of a novel P2X7R radioligand [18F]IUR-1601. / Gao, Mingzhang; Wang, Min; Glick-Wilson, Barbara E.; Meyer, Jill A.; Peters, Jonathan S.; Territo, Paul; Green, Mark; Hutchins, Gary; Zarrinmayeh, Hamideh; Zheng, Qi-Huang.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 28, No. 9, 15.05.2018, p. 1603-1609.

Research output: Contribution to journalArticle

Gao, Mingzhang ; Wang, Min ; Glick-Wilson, Barbara E. ; Meyer, Jill A. ; Peters, Jonathan S. ; Territo, Paul ; Green, Mark ; Hutchins, Gary ; Zarrinmayeh, Hamideh ; Zheng, Qi-Huang. / Synthesis and preliminary biological evaluation of a novel P2X7R radioligand [18F]IUR-1601. In: Bioorganic and Medicinal Chemistry Letters. 2018 ; Vol. 28, No. 9. pp. 1603-1609.
@article{bff8c3cbb11146fca786a48bda414fca,
title = "Synthesis and preliminary biological evaluation of a novel P2X7R radioligand [18F]IUR-1601",
abstract = "The 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.",
keywords = "Competitive binding assay, Positron emission tomography (PET), Purinergic P2X7 receptor (P2X7R), Radiosynthesis, [F]IUR-1601 ((S)-N-(2-chloro-3-(trifluoromethyl)benzyl)-1-(2-[F]fluoroethyl)-5-oxopyrrolidine-2-carboxamide)",
author = "Mingzhang Gao and Min Wang and Glick-Wilson, {Barbara E.} and Meyer, {Jill A.} and Peters, {Jonathan S.} and Paul Territo and Mark Green and Gary Hutchins and Hamideh Zarrinmayeh and Qi-Huang Zheng",
year = "2018",
month = "5",
day = "15",
doi = "10.1016/j.bmcl.2018.03.044",
language = "English (US)",
volume = "28",
pages = "1603--1609",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "9",

}

TY - JOUR

T1 - Synthesis and preliminary biological evaluation of a novel P2X7R radioligand [18F]IUR-1601

AU - Gao, Mingzhang

AU - Wang, Min

AU - Glick-Wilson, Barbara E.

AU - Meyer, Jill A.

AU - Peters, Jonathan S.

AU - Territo, Paul

AU - Green, Mark

AU - Hutchins, Gary

AU - Zarrinmayeh, Hamideh

AU - Zheng, Qi-Huang

PY - 2018/5/15

Y1 - 2018/5/15

N2 - The 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.

AB - The 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.

KW - Competitive binding assay

KW - Positron emission tomography (PET)

KW - Purinergic P2X7 receptor (P2X7R)

KW - Radiosynthesis

KW - [F]IUR-1601 ((S)-N-(2-chloro-3-(trifluoromethyl)benzyl)-1-(2-[F]fluoroethyl)-5-oxopyrrolidine-2-carboxamide)

UR - http://www.scopus.com/inward/record.url?scp=85045005474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045005474&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2018.03.044

DO - 10.1016/j.bmcl.2018.03.044

M3 - Article

VL - 28

SP - 1603

EP - 1609

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 9

ER -