放射合成
化学
trk受体
嘧啶
原肌球蛋白受体激酶B
原肌球蛋白受体激酶A
原肌球蛋白受体激酶C
立体化学
化学合成
受体
生物化学
神经营养素
体外
正电子发射断层摄影术
血小板源性生长因子受体
神经营养因子
生长因子
医学
放射科
作者
Vadim Bernard‐Gauthier,Ralf Schirrmacher
标识
DOI:10.1016/j.bmcl.2014.09.014
摘要
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 [(18)F]10 was developed. The results obtained from the biological evaluation of 10 and the radiosynthesis of [(18)F]10 support further investigation of this tracer as a potential PET imaging probe for TrkB/TrkC and CSF-1R.
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