Synthesis and in vitro evaluation of (S)-2-([11C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-benzoic acid ([11C]methoxy-repaglinide): a potential beta-cell imaging agent.

Björn Wängler, Carmen Beck, Chyng Yann Shiue, Stephan Schneider, Christina Schwanstecher, Mathias Schwanstecher, Peter Johannes Feilen, Abass Alavi, Frank Rösch, Ralf Schirrmacher

Institute of Nuclear Chemistry, University of Mainz, Mainz, Germany.

Bioorganic & medicinal chemistry letters 2004 Oct 18

filter terms:

The 11C-labeled sulfonylurea receptor 1 (SUR1) ligand (S)-2-([11C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-benzoic acid ([11C]methoxy-repaglinide) was synthesized in an overall radiochemical yield of 35% after 55 min with a radiochemical purity higher than 99%. This compound is considered for the noninvasive investigation of the SUR1 receptor status of pancreatic beta-cells by positron emission tomography (PET) in the context of type 1 and type 2 diabetes. The specific activity was 40-70 GBq/micromol. In vitro testing of the nonradioactive methoxy-repaglinide was performed to characterize the affinity for binding to the human SUR1 isoform. Methoxy-repaglinide induced a complete monophasic inhibition curve with a Hill coefficient close to 1 (1.03) yielding a dissociation constant (KD) of 83 nM and an IC50 of 163 nM. Insulin secretion experiments on isolated rat islets were performed to prove biological activity, which was determined to be in the same range as that of original repaglinide.

Citation

Björn Wängler, Carmen Beck, Chyng Yann Shiue, Stephan Schneider, Christina Schwanstecher, Mathias Schwanstecher, Peter Johannes Feilen, Abass Alavi, Frank Rösch, Ralf Schirrmacher. Synthesis and in vitro evaluation of (S)-2-([11C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-benzoic acid ([11C]methoxy-repaglinide): a potential beta-cell imaging agent. Bioorganic & medicinal chemistry letters. 2004 Oct 18;14(20):5205-9