Synthesis of [11C]CX-6258 as a new PET tracer for imaging of Pim kinases in cancer

Abstract

The reference standard CX-6258 {(E)-5-chloro-3-((5-(3-(4-methyl-1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)indolin-2-one, 4a} and its desmethylated precursor N-desmethyl-CX-6258 {(E)-3-((5-(3-(1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)-5-chloroindolin-2-one, 5} for radiolabeling were synthesized from 5-bromo-2-furaldehyde and 3-carboxybenzeneboronic acid in 3 and 4 steps with 29-49% and 24-32% overall chemical yield, respectively. The target tracer [(11)C]CX-6258 {(E)-5-chloro-3-((5-(3-(4-[(11)C]methyl-1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)indolin-2-one, [(11)C]4a} was prepared from N-desmethyl-CX-6258 (5) with [(11)C]CH3OTf under basic condition (2N NaOH) through N-[(11)C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 40-50% radiochemical yield based on [(11)C]CO2 and decay corrected to end of bombardment (EOB) with 370-1110GBq/μmol specific activity at EOB.

Keywords: Cancer; Pim kinases; Positron emission tomography (PET); Radiosynthesis; [(11)C]CX-6258.