Synthesis, fluorescence properties of novel thiazolo[3,2-b][1,2,4]triazol derivatives as potent SHP2 inhibitors and its uses in sensing for Fe3+ and cell imaging

作者: Gao, Li-Xin ; Yan, Xue ; Li, Jia ; Cao, Zi-Tong ; Zhou, Yu-Bo ; Gan, Su-Ya ; Wang, Wen-Long ; Zhang, Chun ; Xiang, Da-Jun

A series of thiazolo[3,2-b][1,2,4]triazole derivatives containing salicylic acid fragment were designed and synthesized.Then, their optical properties and biol. activities were evaluated.Among them, the representative compound 5-2k exhibited higher selectivity/specificity for Fe3+, a low limit of detection (LOD) of 8.2 μM and moderate inhibitory activity against SHP2 with IC50 of 2.85±0.50 μM.Moreover, the activities of SHP1, SHP2, PTP1B and TCPTP enzyme could be adjusted effectively through the interaction between compound 5-2k and metal ion Fe3+.Furthermore, compound 5-2k had low cytotoxicity for peripheral blood mononuclear cell (PBMC) and excellent blue signal in HeLa cell imaging.These results are expected to facilitate the development of novel sensitive and specific fluorescence sensors for Fe3+ and SHP2 inhibitor for cancer therapy.

2025-02-24·Angewandte Chemie International Edition

Electrochemical Cyclopropanation of Unactivated Alkenes with Methylene Compounds

Article

作者: Zhu, Zile ; Jia, Jingpei ; Liu, Min ; Qiu, Youai ; Gao, Chao ; Wang, Yanwei

AbstractCyclopropanes are prevalent in natural products, pharmaceuticals, and bioactive compounds, functioning as a significant structural motif. Although a series of methods have been developed for the construction of the cyclopropane skeleton, the development of a direct and efficient strategy for the rapid synthesis of cyclopropanes from bench‐stable starting materials with a broad substrate scope and functional group tolerance remains challenging and highly desirable. Herein, we present an electrochemical method for the direct cyclopropanation of unactivated alkenes using active methylene compounds. The strategy shows a broad substrate scope with a high level of functional group compatibility, as well as potential application as demonstrated by late‐stage cyclopropanation of complex molecules and drug derivatives. Further mechanistic investigations suggest that Cp2Fe (Fc) plays an essential role as an oxidative mediator in generating radicals from active methylene compounds.

2025-02-01·Journal of Catalysis

Access to cyclobutane–fused dihydrobenzothiophenes via gold–mediated photocatalyzed [2+2]–cycloaddition reactions

作者: Villa, Marco ; Nolan, Steven P. ; Ceroni, Paola ; Martynova, Ekaterina A. ; Hecke, Kristof Van ; Voloshkin, Vladislav V. ; Belis, Marek ; Fiorentino, Antonio

The use of [Au(SIPr)(Cbz)] as photosensitizer in [2+2]-cycloaddition reactions between benzothiophenes and activated and non-activated alkenes is presented.Commonly used organic and Ir-photosensitizers proved inefficient in the reaction with non-activated alkenes.The study emphasizes the dependence on the nature of the alkene, a parameter that has previously received little attention.Under mild reaction conditions, a wide array of alkenes and benzothiophenes were successfully coupled, showcasing remarkable tolerance of diverse functional groups.Addnl., we present intramol. [2+2]-cycloaddition reactions, including benzothiophenes featuring various alkene linkers at the C2 and C3 positions.

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适应症	最高研发状态	国家/地区	公司	日期
高钙血症	临床1期	-	Abeona Therapeutics, Inc.	-
高钙血症	临床1期	-	Colgate-Palmolive Co.	-
畸形性骨炎	临床1期	-	Colgate-Palmolive Co.	-
畸形性骨炎	临床1期	-	Abeona Therapeutics, Inc.	-
绝经期后骨质疏松	临床1期	-	Colgate-Palmolive Co.	-
绝经期后骨质疏松	临床1期	-	Abeona Therapeutics, Inc.	-