33495-30-6

Upstream product

• 90-24-4 2-hydroxy-4,6-dimethoxyacetophenone 
• 98-88-4 benzoyl chloride 
• 480-66-0 2,4,6-trihydroxyacetophenone 
• 500-99-2 3,5-dimethoxyphenol 

Downstream Products

• 21392-57-4 Dimethyl-chrysin 
• 41988-26-5 7-(2-bromoethoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one 
• 1190373-61-5 5-hydroxy-2-phenyl-7-(2-(piperazin-1-yl)ethoxy)-4H-chromen-4-one 
• 1190373-62-6 7-(2-(diethylamino)ethoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one 
• 1190373-63-7 7-(2-(propylamino)ethoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one 
• 1190373-64-8 7-(2-(dipropylamino)ethoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one 
• 1190373-65-9 5-hydroxy-7-(2-(4-methylpiperazin-1-yl)ethoxy)-2-phenyl-4H-chromen-4-one 
• 1190373-66-0 7-(2-(dibutylamino)ethoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one 
• 1190373-67-1 5-hydroxy-2-phenyl-7-(2-(pyrrolidin-1-yl)ethoxy)-4H-chromen-4-one 
• 1190373-69-3 5-hydroxy-2-phenyl-7-(2-(piperidin-1-yl)ethoxy)-4H-chromen-4-one 
• 1236122-77-2 7-(2-(isopropylamino)ethoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one 
• 1236122-78-3 7-(2-(butylamino)ethoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one 
• 1236122-79-4 7-(2-(tert-butylamino)ethoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one 
• 1236122-80-7 7-(2-(diisopropylamino)ethoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one 

Relevant academic research and scientific papers

Novel synthesised flavone derivatives provide significant insight into the structural features required for enhanced anti-proliferative activity

With many cancers showing resistance to current chemotherapies, the search for novel anti-cancer agents is attracting considerable attention. Natural flavonoids have been identified as useful leads in such programmes. However, since an in-depth understanding of the structural requirements for optimum activity is generally lacking, further research is required before the full potential of flavonoids as anti-proliferative agents can be realised. Herein a broad library of 76 methoxy and hydroxy flavones, and their 4-thio analogues, was constructed and their structure-activity relationships for anti-proliferative activity against the breast cancer cell lines MCF-7 (ER +ve), MCF-7/DX (ER +ve, anthracycline resistant) and MDA-MB-231 (ER -ve) were probed. Within this library, 42 compounds were novel, and all compounds were afforded in good yields and >95% purity. The most promising lead compounds, specifically the novel hydroxy 4-thioflavones 15f and 16f, were further evaluated for their anti-proliferative activities against a broader range of cancer cell lines by the National Cancer Institute (NCI), USA and displayed significant growth inhibition profiles (e.g. compound-15f: MCF-7 (GI50 = 0.18 μM), T-47D (GI50 = 0.03 μM) and MDA-MB-468 (GI50 = 0.47 μM) and compound-16f: MCF-7 (GI50 = 1.46 μM), T-47D (GI50 = 1.27 μM) and MDA-MB-231 (GI50 = 1.81 μM)). Overall, 15f and 16f exhibited 7-46 fold greater anti-proliferative potency than the natural flavone chrysin (2d). A systematic structure-activity relationship study against the breast cancer cell lines highlighted that free hydroxyl groups and the B-ring phenyl groups were essential for enhanced anti-proliferative activities. Substitution of the 4-CO functionality with a 4-CS functionality, and incorporation of electron withdrawing groups at C-4′ of the B-ring phenyl, also enhanced activity. Molecular docking and mechanistic studies suggest that the anti-proliferative effects of flavones 15f and 16f are mediated via ER-independent cleavage of PARP and downregulation of GSK-3β for MCF-7 and MCF-7/DX cell lines. For the MDA-MB-231 cell line, restoration of the wild-type p53 DNA binding activity of mutant p53 tumour suppressor gene was indicated.

Synthesis and anti-inflammatory in vitro, in silico, and in vivo studies of flavone analogues

Chrysin and 7-hydroxy flavone were prepared by Baker-Venkatraman rearrangement followed by esterification at 7th position and replacement of ester with acetamide linking to different heterocyclic moieties synthesized 13a-g and 14a-g series of flavones analogues. These were screened against COX-2 and COX-1 enzymes for inhibition by in vitro assay and COX-2 for in silico docking studies. The compound 14a was found to be most active with IC50 of 3.11 μM concentration, with highest binding energy of -12.4 kcal/mole and 77.2 and 80.5 % inhibition at 3 and 5 h post-carrageenan induced in paw oedema.

Synthesis and cytotoxicity of novel chrysin derivatives

A series of chrysin derivatives 8a-8v were prepared and tested in vitro against HCT-116 (human colon cancer cell line), Hela (human cervical carcinoma cell line), DU-145 (human prostate cell line), K562 (human leukemia cell line), and SGC-7901 (human gastric cancer cell line). The chemical structures of these compounds were confirmed by means of MS, IR, 1H NMR, 13C NMR, and elemental analysis. Among these derivatives, 7-(2-(piperazin-1- yl)ethoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one, 8n, had the strongest activity against HCT-116, Hela, DU-145, K562, and SGC-7901 cells. Springer Science+Business Media, LLC 2010.

Antispasmodic activity of xanthoxyline derivatives: Structure-activity relationships

The antispasmodic activity of several xanthoxyline derivatives against acetylcholine-induced contraction of the guinea pig ileum was evaluated in vitro. The acetophenones with two methoxyl groups, mainly in the 3,4 positions, exhibited potent antispasmodic activity. Modification of the hydroxyl group in xanthoxyline by the introduction of benzoyl, acetyl, or tosyl groups produced inactive compounds, whereas the introduction of benzyl or p-methoxybenzyl groups furnished compounds that were four- to eight-fold more potent than xanthoxyline. In marked contrast, the introduction of a methyl group gave a compound that caused contractant activity. Modification of the carbonyl group of xanthoxyline lead to inactive compounds, whereas the condensation of xanthoxyline with benzaldehydes gave chalkones that were about fivefold more potent than xanthoxyline. The introduction of benzyl and styrene groups, on the basis of the similarity with papaverine, improves the antispasmodic action of the xanthoxyline derivatives. Our results suggest that the methoxyl and carbonyl groups are critical structural points for the antispasmodic activity of xanthoxyline derivatives. The hydroxyl group improves antispasmodic activity, but is not fundamental to its manifestation.

Structural Studies on Bio-active Compounds. Part 12. Tautomerism and Conformation of Aryl-substituted 1-(2-Hydroxyphenyl)-3-phenylpropane-1,3-diones in the Solid Phase and in Solution

The tautomerism of a series of aryl-substituted 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-diones has been studied in deuteriochloroform solution by 1H n.m.r. techniques and, in the case of 1-(2-hydroxy-4-methoxyphenyl)-3-phenylpropane-1,3-dione and 1-(2-hydroxy-4,6-dimethoxyphenyl)-3-phenylpropane-1,3-dione, in the solid state by X-ray crystallography.Of these compounds, most exist between 80 and 95percent in the enolised form in solution and 1-(2-hydroxy-4-methoxyphenyl)-3-phenylpropane-1,3-dione adopts this tautomer in the crystal.However, 1-(2-hydroxy-4,6-dimethoxyphenyl)-3-phenylpropane-1,3-dione is present as the diketone in the solid phase and enolises very slowly in solution. 1-(6-Benzoyloxy-2-hydroxyphenyl)-3-hydroxy-3-phenylprop-2-en-1-one is shown by 1H n.m.r. spectroscopy possibly to adopt a 'coiled' conformation in solution in deuteriochloroform.