2020) Design, synthesis and biological evaluation of novel 1H-1,2,4-triazole, benzothiazole and indazole-based derivatives as potent FGFR1 inhibitors viafragment-based virtual screening, Journal of Enzyme Inhibition and Medicinal Chemistry, 35:1, 72-84, ABSTRACTFibroblast growth-factor receptor (FGFR) is a potential target for cancer therapy. We designed three novel series of FGFR1 inhibitors bearing indazole, benzothiazole, and 1H-1,2,4-triazole scaffold via fragmentbased virtual screening. All the newly synthesised compounds were evaluated in vitro for their inhibitory activities against FGFR1. Compound 9d bearing an indazole scaffold was first identified as a hit compound, with excellent kinase inhibitory activity (IC 50 ¼ 15.0 nM) and modest anti-proliferative activity (IC 50 ¼ 785.8 nM). Through two rounds of optimisation, the indazole derivative 9 u stood out as the most potent FGFR1 inhibitors with the best enzyme inhibitory activity (IC 50 ¼ 3.3 nM) and cellular activity (IC 50 ¼ 468.2 nM). Moreover, 9 u also exhibited good kinase selectivity. In addition, molecular docking study was performed to investigate the binding mode between target compounds and FGFR1. GRAPHICAL ABSTRACT ARTICLE HISTORY

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.

In this study, we report a novel and efficient synthetic method to construct isoquinolone scaffold via the Rh­(III)-catalyzed (4 + 2) annulation of benzamide with an unreported coupling reagent methyl 2-chloroacrylate. Accordingly, other valuable 1,2-benzothiazine and naphtho­[1′,2′:4,5]­imidazo­[1,2-a]­pyridine derivatives are also obtained through a similar synthetic protocol. Thus, our developed method is highlighted by high yield and reaction versatility.