Guo Lin,Yang Shu-Qing,Zhao Kai-Chun,Chen Xiao-Chao,Lu Yong,Liu Ye
The structures of 2,5-diaryl-1,3,4-oxadiazoles with good stability have attract great attention for development of new and safe therapeutic agents with functions in antimicrobial, anti-inflammatory, antitumor, and antiviral (for treatment of HIV infection), etc. In the present work, over the developed Pd-catalytic system with involvement of the 3-thiophenyl-benzimidazolyl-based mono-phosphine, the one-pot carbonylation-dehydration tandem reaction of aryl iodides with acylhydrazines for synthesis of 2,5-diaryl-1,3,4-oxadiazoles was reported for the first time with advantages of simplified manipulations, high efficiency (yields of 62–93%), as well as high safety of applied organic substrates. The relatively high reaction temperature of 140–160 ℃ was required for this tandem reaction, wherein the good stability of the involved phosphine with suitable stereo-electronic property guaranteed the fulfilment of this sequence. It was demonstrated that the first-step carbonylation of aryl iodides with acylhydrazine toward N , N′- diarylhydrazides was the rate-determine step in the overall process. Subsequently, the formed N , N' -dibenzoylhydrazides irreversible dehydrated into 2,5-diaryl-1,3,4-oxadiazoles with the presence of dehydrating agent like DCC. Graphical abstract
Aim: The first inhibitor targeting myoferlin (MYOF), WJ460, bears poor metabolic stability and water solubility. Therefore, this study aimed to improve the drug-like properties of WJ460. Materials & methods: The authors synthesized an array of 1,5-diaryl-1,2,4-triazole analogs and appraised the binding activities with MYOF and their antiproliferative and antimigratory activities against pancreatic cancer cells. Results: Molecular docking and surface plasmon resonance results showed that E4 was directly bound to the MYOF-C2D domain. E4 effectively inhibited the proliferation and migration of pancreatic cancer cells in vitro. An in silico study suggested that the water solubility of E4 was improved by about 22-times than that of WJ460. Conclusion: The findings suggested that the druglike ability of E4 was significantly improved.Graphical abstract
危险品化学品经营许可证（带存储）