New 8-chloro-2-phenyl-2,7-naphthyridin-1(2H)-one building blocks bearing diverse substitutes on the 2-phenyl group were synthesized via an efficient diaryliodonium salt-based N-arylation strategy with the advantage of mild conditions, short reaction times, and high yields. A small combinatorial library of 8-amino substituted 2-phenyl-2,7-naphthyridin-1(2H)-one was further conveniently constructed based on the above chlorinated naphthyridinones and substituted aniline. Preliminary biochemical screening resulted in the discovery of the new 2,7-naphthyridone-based MET/AXL kinase inhibitors. More importantly, 17c (IC_50,MET of 13.8 nM) or 17e (IC_50,AXl of 17.2 nM) and 17i (IC_50,AXl of 31.8 nM) can efficient selectively inhibit MET or AXL kinase, respectively, while commercial cabozantinib showed no selectivity. The further exploration of the 8-substituted 2-phenyl-2,7-naphthyridin-1(2H)-one combinatorial library would significantly accelerate the discovery of more potent and selective inhibitors against diverse kinases.

中文翻译：

---

2,7-Naphthyridin-1(2H)-one 与 Diaryliodonium 盐的有效芳基化和新型选择性 MET/AXL 激酶抑制剂的发现。

新型 8-chloro-2-phenyl-2,7-naphthyridin-1(2 H )-one 结构单元在 2-苯基上带有不同的取代基，通过基于二芳基碘盐的高效N-芳基化策略合成，具有以下优点：条件温和，反应时间短，产率高。基于上述氯化萘啶酮和取代苯胺，进一步方便地构建了一个8-氨基取代的2-苯基-2,7-萘啶-1(2 H )-one的小型组合库。初步生化筛选导致发现了新的基于 2,7-萘啶酮的 MET/AXL 激酶抑制剂。更重要的是，17c（IC _50，MET为 13.8 nM）或17e（IC _50，AXl17.2 nM) 和17i (IC _{50, AXl}为 31.8 nM) 可以分别有效地选择性抑制 MET 或 AXL 激酶，而市售的卡博替尼没有表现出选择性。进一步探索 8-取代的 2-苯基-2,7-naphthyridin-1(2 H )-one 组合文库将显着加速发现针对多种激酶的更有效和选择性抑制剂。