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.

• Authors: Min Wang, Reynaldo Tzintzun, Mingzhang Gao, Zhidong Xu, Qi-Huang Zheng
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 25 Issue 18 Pg. 3831-5 (Sep 15 2015) ISSN: 1464-3405 [Electronic] England
• PMID: 26227775 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Azepines
• CX-6258
• Carbon Radioisotopes
• Indoles
• Radiopharmaceuticals
• Proto-Oncogene Proteins c-pim-1
• proto-oncogene proteins pim

Topics

• Azepines (chemical synthesis, chemistry, pharmacology)
• Carbon Radioisotopes
• Chromatography, High Pressure Liquid
• Humans
• Indoles (chemical synthesis, chemistry, pharmacology)
• Molecular Structure
• Neoplasms (diagnostic imaging, enzymology)
• Positron-Emission Tomography
• Proto-Oncogene Proteins c-pim-1 (metabolism)
• Radiopharmaceuticals (chemical synthesis, chemistry, pharmacology)