94300-99-9Relevant academic research and scientific papers
Construction and activity evaluation of novel dual-target (SE/CYP51) anti-fungal agents containing amide naphthyl structure
An, Yunfei,Fan, Haiyan,Han, Jun,Liu, Wenxia,Liu, Yating,Sun, Bin,Sun, Zhuang
, (2021/11/16)
With the increase of fungal infection and drug resistance, it is becoming an urgent task to discover the highly effective antifungal drugs. In the study, we selected the key ergosterol bio-synthetic enzymes (Squalene epoxidase, SE; 14 α-demethylase, CYP51) as dual-target receptors to guide the construction of novel antifungal compounds, which could achieve the purpose of improving drug efficacy and reducing drug-resistance. Three different series of amide naphthyl compounds were generated through the method of skeleton growth, and their corresponding target products were synthesized. Most of compounds displayed the obvious biological activity against different Candida spp. and Aspergillus fumigatus. Among of them, target compounds 14a-2 and 20b-2 not only possessed the excellent broad-spectrum anti-fungal activity (MIC50, 0.125–2 μg/mL), but also maintained the anti-drug-resistant fungal activity (MIC50, 1–4 μg/mL). Preliminary mechanism study revealed the compounds (14a-2, 20b-2) could block the bio-synthetic pathway of ergosterol by inhibiting the dual-target (SE/CYP51) activity, and this finally caused the cleavage and death of fungal cells. In addition, we also discovered that compounds 14a-2 and 20b-2 with low toxic and side effects could exert the excellent therapeutic effect in mice model of fungal infection, which was worthy for further in-depth study.
Synthesis method of alpha-acylamino ketone compound
-
Paragraph 0027-0029; 0030-0032; 0098, (2020/12/08)
The invention discloses a synthesis method of an alpha-acylamino ketone compound, and belongs to the technical field of organic synthesis. The preparation method comprises the following steps: mixingan alkenyl azide compound 1, a carboxylic acid compound 2 and an organic solvent, and heating to react to obtain the alpha-acylamino ketone compound 3. Compared with the prior art, the method has thefollowing advantages: (1) the synthesis process is simple and efficient, no catalyst is needed in the whole process, and the alpha-acylamino ketone compound can be obtained with high yield by dissolving the alkenyl azide compound and the carboxylic acid compound in the solvent and stirring; (2) raw materials are cheap and easy to obtain, reaction conditions are mild, and operation is simple; (3) the substrate is wide in application range and can be used for modifying drug molecules; and (4) the atom economy is high, and the requirements of green chemistry are met.
