Synthesis and in vitro evaluation of [[super]18F]fluoroethyl triazole labelled [Tyr[super]3]octreotate analogues using click chemistry

A novel class of alkyne linked [Tyr[super]3]octreotate analogues have been labelled by a copper catalysed azide-alkyne cycloaddition reaction (CuAAC) to form a 1,4-substituted triazole using the reagent [[super]18F]2-fluoroethyl azide. An unexpected variability in reactivity during the CuAAC reactio...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2011-05, Vol.21 (10), p.3122-3127
Hauptverfasser: Iddon, Lisa, Leyton, Julius, Indrevoll, Baard, Glaser, Matthias, Robins, Edward G, George, Andrew JT, Cuthbertson, Alan, Luthra, Sajinder Kaur, Aboagye, Eric O
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Sprache:eng
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Zusammenfassung:A novel class of alkyne linked [Tyr[super]3]octreotate analogues have been labelled by a copper catalysed azide-alkyne cycloaddition reaction (CuAAC) to form a 1,4-substituted triazole using the reagent [[super]18F]2-fluoroethyl azide. An unexpected variability in reactivity during the CuAAC reaction was observed for each alkyne analogue which has been investigated. Two lead alkyne linked [Tyr[super]3]octreotate analogues, G-TOCA ( 3a) and beta AG-TOCA ( 5a) have been identified to be highly reactive in the click reaction showing complete conversion to the [[super]18F]2-fluoroethyl triazole linked [Tyr[super]3]octreotate analogues FET-G-TOCA ( 3b) and FET- beta AG-TOCA ( 5b) under mild conditions and with short synthesis times (5 min at 20 [deg]C). As well as ease of synthesis, in vitro binding to the pancreatic tumour AR42J cells showed that both FET-G-TOCA and FET- beta AG-TOCA have high affinity for the somatostatin receptor with IC sub(50 of 4.0 +/- 1.4, and 1.6 +/- 0.2 nM, respectively.)
ISSN:0960-894X
DOI:10.1016/j.bmcl.2011.03.016