Fibroblast growth factor receptor 4 (FGFR4) has been identified as a potential target due to its transmission of the FGF19 signaling pathway, which is critical to hepatocellular carcinoma (HCC). Therefore, focusing on the specific Cys552 of FGFR4 subtype, we designed and synthesized a novel family of 1,6-naphthyridin-2­(1H)-one derivatives as potent and highly selective FGFR4 inhibitors. Through detailed structural optimizations, the representative compound A34 exhibited improved FGFR4 inhibitory capability and selectivity and excellent anti-proliferative activities against FGFR4-dependent HCC cell lines. Additionally, A34 demonstrated remarkable antitumor efficacy in a Hep-3B HCC xenograft model, with favorable pharmacokinetic properties, and low risk of hERG toxicity. A34 also showed moderate inhibitory activities against the FGFR4 V550L mutant in vitro, which indicates that it has the potential as a novel anticancer agent for HCC.

A one-pot and step economic reaction involving Rh­(III)-catalyzed C–H thiolation and relay Cu­(II)-catalyzed C–N amination of acetanilide and 2-bromothiophenol is reported here, with several valuable phenothiazine products obtained. This synthesis protocol proceeds from easily starting materials, demonstrating high atom economy, broad substrate scope, and good yield. Furthermore, the directing group can be easily eliminated, and chlorpromazine is provided in a large scale; thus this synthesis protocol could be utilized to construct phenothiazine scaffolds.

The analogous three‐component synthesis strategy for substituted 1,2,4‐oxadiazole and quinazoline derivatives from readily available benzaldehyde, benzylamine and hydroxylamine or aniline has been developed. Both the cascade reaction sequences involves nucleophilic addition of C−N bond, introduction a halogen donor, nucleophilic substitution and Cu(II)‐catalyzed aerobic oxidation. This synthesis methodology demonstrated good yields, broad substrate scope and oxygen as a green oxidant. Thus, this synthesis protocol provides strategies for the construction of substituted 1,2,4‐oxadiazole and quinazolines from readily and simple starting materials.

We established an efficient and sustainable rhodium(III)-catalyzed and ionic liquid-mediated CÀ S and CÀ Se formation from readily available starting material acetanilide with diaryl disulfides and diaryl diselenides. The CÀ H activation proceeds in ionic liquid without extra silver salt as additive, and the catalytic media can be reused for several times to accomplish the catalysts sustainable utilization. Furthermore, this synthesis protocol is suitable for a wide functional group compatibility, and the directing group can be easily removed. Most importantly it can be developed as a facile access to phenothiazine scaffold with potent biological activities, thus this strategy can be broadly applied to organic synthesis and medicinal chemistry.

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The C−H annulation of the five-position of quinolines and acrylates to afford heterocycles is an active field of research in organic synthesis. Herein the annulation of 4aminoquinolines with acrylates through two consecutive C−H activations catalyzed by Rh(III) is described. The reaction proceeds with high atom efficiency under mild reaction conditions, and this protocol will provide appealing strategies for the synthesis of fused quinoline heterocycles.Letter pubs.acs.org/OrgLett

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