Design and synthesis of [(125)I]Pyricoxib: A novel (125)I-labeled cyclooxygenase-2 (COX-2) inhibitors

Bioorganic & Medicinal Chemistry Letters
Ole TietzFrank Wuest

Abstract

Cyclooxygenase-2 (COX-2) is the key enzyme in the prostaglandin synthesis pathway which is involved in various pathophysiological conditions. The enzyme is membrane bound and located inside of the endoplasmic reticulum and nuclear membrane. Effective perfusion of inhibitors to the active site requires lipophilic drugs, which consequently display high unspecific background accumulation, for example, in fatty tissues. The objective of this work was the development of a small molecule radiolabeled with a long-lived iodine radioisotope to enable longer imaging times and better target-to-background ratios. A group of iodinated compounds (8-10) was synthesized and identified as selective COX-2 inhibitors (COX-2 IC50=0.85-13 μM). Molecular docking results provided the theoretical support for the experimental COX-2 inhibition data. Furthermore, a novel (125)I-containing trifluoro-pyrimidine compound ([(125)I]Pyricoxib) was prepared via radioiododestannylation reaction as potent and selective COX-2 inhibitor. Radiosynthesis of [(125)I]Pyricoxib was accomplished with innovative fluorous chemistry using fluorous chloroamine-T (F-CAT) as novel oxidizing agent in high radiochemical yields of 91 ± 4%.

References

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Sep 26, 2013·Current Medicinal Chemistry·O TietzF Wuest
Oct 23, 2013·Organic & Biomolecular Chemistry·Ole TietzFrank Wuest
Jan 29, 2014·Journal of Labelled Compounds & Radiopharmaceuticals·A PacelliG Smith
Jul 30, 2014·Journal of Labelled Compounds & Radiopharmaceuticals·James P K DzandziJohn F Valliant

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Citations

Jul 8, 2016·Organic & Biomolecular Chemistry·Ole TietzFrank R Wuest
Feb 15, 2019·Journal of Chemical Information and Modeling·Zijian QinAixia Yan

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