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Synlett 2018; 29(11): 1491-1495
DOI: 10.1055/s-0036-1591985
letter
© Georg Thieme Verlag Stuttgart · New York

Copper-Mediated Late-Stage Iodination and 123I-Labelling of Triazole-benzimidazole Bioactives

Richard Fjellaksel
a   Medical Imaging Group, Department of Clinical Medicine, UiT The Arctic University of Norway, 9037 Tromsø, Norway
b   Drug Transport and Delivery Group, Department of Pharmacy, UiT The Arctic University of Norway, 9037 Tromsø, Norway
c   Organic Chemistry Group, Department of Chemistry, UiT The Arctic University of Norway, 9037 Tromsø, Norway   Email: jorn.h.hansen@uit.no
,
Rune Sundset
a   Medical Imaging Group, Department of Clinical Medicine, UiT The Arctic University of Norway, 9037 Tromsø, Norway
d   PET imaging center, Division of Diagnostics, UNN – University Hospital of North-Norway, 9038 Tromsø, Norway
,
Patrick J. Riss
e   Department of Neuropsychiatry and Psychosomatic Medicine, Oslo University Hospital, Oslo, Norway
f   Realomics SFI, Department of Chemistry, University of Oslo, PO BOX 1033, Oslo 0371, Norway
g   Norsk Medisinsk Syklotronsenter AS, Postboks 4950 Nydalen, Oslo 0424, Norway
,
Jørn H. Hansen*
c   Organic Chemistry Group, Department of Chemistry, UiT The Arctic University of Norway, 9037 Tromsø, Norway   Email: jorn.h.hansen@uit.no
› Author AffiliationsR.F. and R.S. acknowledge the Northern Norway Regional Health Authority (SFP1196-14). P.J.R. gratefully acknowledges the Research Council of Norway and the University of Oslo (Realomics SFI). J.H.H. gratefully acknowledges the Department of Chemistry at UiT The Arctic University of Norway, for funding parts of this research project.
Further Information

Publication History

Received: 03 January 2018

Accepted after revision: 15 March 2018

Publication Date:
19 April 2018 (online)

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Abstract

The copper-mediated azide-alkyne cycloaddition has been studied to achieve late-stage introduction of iodine onto novel triazole-benzimidazole Gonadotropin Releasing Hormone (GnRH)-receptor antagonists. Moreover, the reaction conditions can affect a direct regioselective C–H iodination of the benzimidazole, leading to a range of novel iodo-analogues. The methodologies are powerful strategies for late-stage 123I-labelling of complex bioactives. Our investigations have generated two highly promising 123I-labelled radiotracer candidates that retain high affinities for the GnRH-receptor.

Key words

CuAAC - GnRH antagonist - radiotracer - triazoles - 123I-labeling

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1591985.
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  • References and Notes

  • 1 Maschauer S. Prante O. BioMed Res. Int. 2014; 16
  • 2 Yan R. Sander K. Galante E. Rajkumar V. Badar A. Robson M. El-Emir E. Lythgoe MF. Pedley RB. Arstad E. J. Am. Chem. Soc. 2013; 135: 703
    CrossrefPubMed
  • 3 Choi JY. Lee BC. Nucl. Med. Mol. Imaging 2015; 49: 258
    CrossrefPubMed
  • 4 Fjellaksel R. Boomgaren M. Sundset R. Haraldsen IH. Hansen JH. Riss PJ. MedChemComm 2017; 8: 1965
    CrossrefPubMed
  • 5 Pelletier JC. Chengalvala MV. Cottom JE. Feingold IB. Green DM. Hauze DB. Huselton CA. Jetter JW. Kopf GS. Lundquist JT. Magolda RL. Mann CW. Mehlmann JF. Rogers JF. Shanno LK. Adams WR. Tio CO. Wrobel JE. J. Med. Chem. 2009; 52: 2148
    CrossrefPubMed
  • 6 Koehler L. Gagnon K. McQuarrie S. Wuest F. Molecules 2010; 15
  • 7 Mettler Jr FA. Guiberteau MJ. In Essentials of Nuclear Medicine Imaging (Sixth Edition) . Saunders WB. Elsevier; Philadelphia: 2012: 99-130 DOI: 10.1016/B978-1-4557-0104-9.00004-4
    Google Scholar
  • 8 Brotherton WS. Clark RJ. Zhu L. J. Org. Chem. 2012; 77: 6443
    Crossref
  • 9 Smith NW. Polenz BP. Johnson SB. Dzyuba SV. Tetrahedron Lett. 2010; 51: 550
    Crossref
  • 10 Worrell BT. Malik JA. Fokin VV. Science 2013; 340: 457
    Crossref
  • 11 Li L. Hao G. Zhu A. Liu S. Zhang G. Tetrahedron Lett. 2013; 54: 6057
    Crossref
  • 12 Iodination at the 7-Position on the Benzimidazole; Typical Procedure for Compound 4: Compound 1 (10 mg, 1.0 equiv, 0.027 mmol) was added to a solution of 2-fluoroethyl azide (0.26 mL, 28 mg/mL, 0.081 mmol, 3.0 equiv), Cu(ClO4)2·6H2O (10 mg, 0.027 mmol, 1.0 equiv), pyridine (2.1 mg, 0.027 mmol, 1.0 equiv) in H2O/THF (1:9, 3 mL). NaI (4.1 mg, 0.027 mmol, 1.0 equiv) was then added and the mixture was heated and stirred for 1 h at 100 °C. The product was lyophilized to afford 2 (5.9 mg, 38% yield) as a white powder. 1H NMR (400 MHz, methanol-d 4): δ = 8.30 (s, 1 H), 8.10 (d, J = 8.2 Hz, 2 H), 7.64 (d, J = 8.4 Hz, 3 H), 6.74 (d, J = 8.3 Hz, 1 H), 4.81 (s, 2 H), 4.64 (s, 2 H), 3.66 (br s, 8 H), 1.41 (s, 9 H); HRMS (ESI): m/z [M+H]+ calcd 588.1742; found: 588.1743
  • 13 Cheng Y.-C. Prusoff WH. Biochem. Pharmacol. 1973; 22: 3099
    Crossref