501-94-0Relevant articles and documents
Inouye et al.
, p. 2029 (1975)
Discovery of novel 2,3,5-trisubstituted pyridine analogs as potent inhibitors of IL-1β via modulation of the p38 MAPK signaling pathway
Campos, Pedro M.,Carrasco, Esther,Gomez-Gutierrez, Patricia,Messeguer, Angel,Perez, Juan J.,Vega, Miguel
, (2021/07/28)
Interleukin-1β is a central mediator of innate immune responses and inflammation. It plays a key role in a wide variety of pathologies, ranging from autoinflammatory diseases to metabolic syndrome and malignant tumors. It is well established that its inhibition results in a rapid and sustained reduction in disease severity, underlining the importance of having a repertoire of drugs of this class. At present, there are only three interleukin-1β blockers approved in the clinic. All of them are biologics, requiring parenteral administration and resulting in expensive treatments. In an exercise to identify small molecule allosteric inhibitors of MAP kinases, we discovered a series of compounds that block IL-1β release produced as a consequence of a stimulus involved in triggering an inflammatory response. The present study reports the hit-to-lead optimization process that permitted the identification of the compound 13b (AIK3-305) an orally available, potent and selective inhibitor of IL-1β. Furthermore, the study also reports the results of an in vivo efficacy study of 13b in a LPS endotoxic shock model in male BALB/c mice, where IL-1β inhibition is monitored in different tissues.
Rapid biosynthesis of phenolic glycosides and their derivatives from biomass-derived hydroxycinnamates
Zhao, Mingtao,Hong, Xulin,Abdullah,Yao, Ruilian,Xiao, Yi
supporting information, p. 838 - 847 (2021/02/09)
Biomass-derived hydroxycinnamates (mainly includingp-coumaric acid and ferulic acid), which are natural sources of aromatic compounds, are highly underutilized resources. There is a need to upgrade them to make them economically feasible. Value-added phenolic glycosides and their derivatives, both belonging to a class of plant aromatic natural products, are widely used in the nutraceutical, pharmaceutical, and cosmetic industries. However, their complex aromatic structures make their efficient biosynthesis a challenging process. To overcome this issue, we created three novel synthetic cascades for the biosynthesis of phenolic glycosides (gastrodin, arbutin, and salidroside) and their derivatives (hydroquinone, tyrosol, hydroxytyrosol, and homovanillyl alcohol) fromp-coumaric acid and ferulic acid. Moreover, because the biomass-derived hydroxycinnamates directly provided aromatic units, the cascades enabled efficient biosynthesis. We achieved substantially high production rates (up to or above 100-fold enhancement) relative to the glucose-based biosynthesis. Given the ubiquity of the aromatic structure in natural products, the use of biomass-derived aromatics should facilitate the rapid biosynthesis of numerous aromatic natural products.
Synthesis method of p-hydroxyphenylethanol
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Paragraph 0033-0037; 0041-0045; 0049-0052, (2020/07/21)
The invention relates to the field of organic synthesis, and discloses a synthesis method of p-hydroxyphenylethanol, which comprises the following steps: (1) mixing methanol, sodium methoxide and a catalyst, and performing stirring; (2) adding 4-chlorophenethyl alcohol, and carrying out a heating reaction; (3) cooling to room temperature, carrying out filtering, and drying by distillation to obtain a 4-methoxyphenethyl alcohol crude product; (4) adding the crude product into a solvent, and performing stirring; (5) dropwise adding hydrobromic acid, carrying out heating reflux, and carrying outa heat preservation reaction until the reaction is finished; (6) cooling to 55-65 DEG C, slowly adding an alkaline solution, and adjusting the pH value to 6-7; and (7) cooling to 8-12 DEG C, stirringfor 0.5-1.5h, filtering the material to obtain a wet filter cake, adding a solvent, heating for dissolution, separating water, and carrying out recrystallizing, filtering, and spin-drying to obtain the final product. The product purity can reach 99% or more, the yield can reach 90% or more, and the whole synthesis process has the advantages of simple and mild reaction conditions, simple post-treatment, and low cost.
