Add time:09/25/2019 Source:sciencedirect.com
The tropomyosin receptor kinases (TrkA/B/C) and colony-stimulating factor-1 receptor (CSF-1R) represent highly pursued oncological therapeutic targets. The 2,4-diaminopyrimidine inhibitor GW2580 (9) has been previously reported as a highly selective low nanomolar TrkB/TrkC/CSF-1R inhibitor. In this study, fluorinated derivatives of 9 were designed, synthesized and evaluated in enzymatic assays. The highly potent inhibitor 10 was identified, which retained the selectivity profile of the non fluorinated lead compound 9, and the radiosynthesis of [18F]10 was developed. The results obtained from the biological evaluation of 10 and the radiosynthesis of [18F]10 support further investigation of this tracer as a potential PET imaging probe for TrkB/TrkC and CSF-1R.
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