500-66-3Relevant articles and documents
Preparation method of 3,5-dihydroxyamylbenzene
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Paragraph 0042-0043; 0047; 0054-0055; 0059, (2021/06/12)
The invention provides a preparation method of 3,5-dihydroxyamylbenzene. The preparation method comprises the following steps: with a 3,5-dialkoxy benzoate compound as a raw material, subjecting the 3,5-dialkoxy benzoate compound to reacting with valeronitrile to generate a beta-ketone nitrile compound, hydrolyzing a cyano group to generate a carboxylic acid compound, performing a decarboxylation reaction to obtain 3,5-dialkoxyphenylpentanone, performing Huang Ming-long reaction or catalytic hydrogenation to convert 3,5-dialkoxyphenylpentanone into 3,5-dialkoxyamylbenzene, and finally, reducing an alkoxy group into a phenolic hydroxyl group so as to obtain 3,5-dihydroxyamylbenzene. The preparation method provided by the invention overcomes the defects of high cost, complex route, low yield, poor purity and the like of traditional processes.
Synthesis, inhibitory activity and in silico docking of dual COX/5-LOX inhibitors with quinone and resorcinol core
Sisa, Miroslav,Dvorakova, Marcela,Temml, Veronika,Jarosova, Veronika,Vanek, Tomas,Landa, Premysl
, (2020/07/31)
Based on the significant anti-inflammatory activity of natural quinone primin (5a), series of 1,4-benzoquinones, hydroquinones, and related resorcinols were designed, synthesized, characterized and tested for their ability to inhibit the activity of cyclooxygenase (COX-1 and COX-2) and 5-lipoxygenase (5-LOX) enzymes. Structural modifications resulted in the identification of two compounds 5b (2-methoxy-6-undecyl-1,4-benzoquinone) and 6b (2-methoxy-6-undecyl-1,4-hydroquinone) as potent dual COX/5-LOX inhibitors. The IC50 values evaluated in vitro using enzymatic assay were for compound 5b IC50 = 1.07, 0.57, and 0.34 μM and for compound 6b IC50 = 1.07, 0.55, and 0.28 μM for COX-1, COX-2, and 5-LOX enzyme, respectively. In addition, compound 6d was identified as the most potent 5-LOX inhibitor (IC50 = 0.14 μM; reference inhibitor zileuton IC50 = 0.66 μM) from the tested compounds while its inhibitory potential against COX enzymes (IC50 = 2.65 and 2.71 μM for COX-1 and COX-2, respectively) was comparable with the reference inhibitor ibuprofen (IC50 = 4.50 and 2.46 μM, respectively). The most important structural modification leading to increased inhibitory activity towards both COXs and 5-LOX was the elongation of alkyl chain in position 6 from 5 to 11 carbons. Moreover, the monoacetylation in ortho position of bromo-hydroquinone 13 led to the discovery of potent (IC50 = 0.17 μM) 5-LOX inhibitor 17 (2-bromo-6-methoxy-1,4-benzoquinone) while bromination stabilized the hydroquinone form. Docking analysis revealed the interaction of compounds with Tyr355 and Arg120 in the catalytic site of COX enzymes, while the hydrophobic parts of the molecules filled the hydrophobic substrate channel leading up to Tyr385. In the allosteric catalytic site of 5-LOX, compounds bound to Tyr142 and formed aromatic interactions with Arg138. Taken together, we identified optimal alkyl chain length for dual COX/5-LOX inhibition and investigated other structural modifications influencing COX and 5-LOX inhibitory activity.
3. 5 - Dihydroxy fifth heavenly stem benzene synthetic method
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, (2019/07/04)
The invention provides a 3, 5 - dihydroxy fifth heavenly stem benzene synthetic method, through under the acid catalysis of benzene with a Friedel - crafts acylation reaction to obtain the [...], the acid is a Lewis acid; the obtained [...] nitration to obtain 3, 5 - dinitrobenzene pentanone; then into methylene carbonyl reduction after reduction of nitro, to obtain 3, 5 - diamino [...]; diazotisations 3, 5 - diamino [...] variable hydroxy obtain 3, 5 - dihydroxy fifth heavenly stem benzene. The invention raw materials used are cheap and easily obtained bulk chemical raw materials, every one-step reaction conditions are relatively mild, which belongs to the chemical industry a large number of applied to the conventional reaction. In accordance with the technique to obtain the final product 3, 5 - dihydroxy fifth heavenly stem benzene (Olivetol) high purity, can reach 98.5% or more, the single hetero in 0.3% to the inner.
