摘要：Acidic oligosaccharide sugar chain （AOSC）, a D-mannuronic acid oligosaccharide, derived from brownalgaepolysaccharide, has been completed Phase I clinical trial in China as an anti-Alzheimer＇s Disease （AD） drug candidate. The identification of AOSC-binding protein（s） in neurons is very important for understanding its action mechanism. To determine the binding protein（s） of AOSC in neurons mediating its anti-AD activities, confocal microscopy, affinity chromatography, and liquid chromatography-tandem mass spectrometry （LC-MS/MS） analysis were used. Confocal microscopy analysis shows that AOSC binds to SH-SY5Y cells in concentration-, time-, and temperature-dependent fashions. The AOSC binding proteins were purified by affinity chromatography and identified by LC-MS/MS analysis. The results showed that there are 349 proteins binding AOSC, including clathrin, adaptor protein-2 （AP-2） and amyloid precursor protein （APP）. These results suggest that the binding/entrance of AOSC to neurons is probably responsible for anti-AD activities.

摘要：Since the PI3K signaling pathway is the most commonly activated in human cancers,inhibition of PI3K is a promising approach to cancer *** this study,a series of 2-methyl-5-nitrobenzeneacylhydrazones were designed and *** the new derivatives were tested by p110α enzymatic and Rh30 cellular *** enzyme selectivity profiling proved that 6e and 7 were potential selective PI3K inhibitors.

摘要：In order to find novel antifungal agents with good activity and aqueous solubility, a series of SYN-2869 analogues containing a pyridine ring were synthesized and evaluated for their in vitro antifungal activity and water solubility. The results indicated that some compounds showed potent activity against six pathogenic fungi. In particular, the analogue 17a having an isobutyl substitution on the triazolone exhibited significant broad spectrum antifungal activity. In addition, the water solubility of compound l？a was sufficiently improved over SYN-2869.

摘要：GPR40 has emerged as an attractive drug target for the treatment of type 2 diabetes due to its role in the enhancement of insulin secretion with glucose dependency. With the aim to improve the metabolic and safety profiles, a series of novel phenylpropionic acid derivatives were synthesized. Extensive structural optimization led to identification of compounds 22 g and 23 e as potent GPR40 agonists with moderate liver microsomal stability. All the discovery supported further exploration surrounding this scaffold.

摘要：A series of novel pleuromutilin derivatives with 4H-pyran-4-one and pyridin-4-one substitution in the C-14 side chain have been designed and synthesized. In vitro antibacterial activity evaluation showed that most of the derivatives exhibited potent antibacterial activity against drug resistant Gram-positive strains. Compounds 12 a, 12 d, and 28 are the most active derivatives in this series, displaying activity comparable to that of retapamulin and BC-3781. As the metabolic stability of this series is not satisfactory, further modifications are going on to improve their pharmacokinetic profile.

摘要：A novel series of pyrido[ 1,2-e]purin-4（3H）-one derivatives containing polar substituents on 5＇-position were designed and prepared as potential PDE5 inhibitors. This paper reports the synthetic routes, 1H-NMR data, and the PDE5 inhibitory activities of the target compounds. The polar piperazinyl group contained （on 5＇-position） compound, 3B2, showed the highest activity among the tested derivatives but less potency than sildenafil 1.

摘要：Inhibition of VEGFR-2 signaling pathway is one of the most promising approaches for the treatment of cancer. In this paper, we reported the design, synthesis, and biological evaluation of a series of biphenylurea derivatives as VEGFR-2 inhibitors. Among these compounds, 39 exhibited potent inhibitory activity against VEGFR-2 both in vitro and in vivo. The antiangiogenesis activity of 39 was further confirmed by both tube formation assay and chick chorioallantoic membrane assay.

摘要：A new series of benzamide derivatives as glucokinase activators （GKAs） were designed and synthesized, and their activation for glucokinase were evaluated by the preliminary glucokinase activity assay. The structure-activity relationship （SAR） is discussed. The result shows that compound 12d and 12h have potent activity reference drug RO-28-1675.

摘要：Inhibition of VEGFR-2 signaling pathway has already become one of the most promising approaches for the treatment of *** this study,we describe the design,synthesis,and biological evaluation of a series of O-linked indoles as potent inhibitors of *** these compounds,18 showed significant anti-angiogenesis activities via VEGFR-2 in enzymatic proliferation assays,with IC50 value of3.8 nmol/L Kinase selectivity profiling revealed that 18 was a multitargeted inhibitor,and it also exhibited good potency against VEGFR-1,PDCFR-α and β.

摘要：A series of novel triazole derivatives containing y-lactam were designed and synthesized, and their structures were confirmed by IH NMR, 13C NMR and HRMS, The in vitro antifungal activities of the target compounds were evaluated, The results showed that all of the compounds exhibited stronger activity against the six clinically important fungi tested than fluconazole. 3D and 3E showed comparative activity against the fungi tested except for Candida glabrata and Aspergillus fumigatus as voriconazole. In addition, the docking model for 2A and CYP51 was investigated.