460744-76-7

Upstream product

• 3535-37-3 3,4-dimethoxybenzoic acid chloride 
• 5396-18-9 2'-hydroxy-3',4'-dimethoxyacetophenone 
• 460744-74-5 6-acetyl-2,3-dimethoxyphenyl-3,4-dimethoxybenzoate 

Downstream Products

• 460744-77-8 1-(3,4-dimethoxyphenyl)-2-fluoro-3-(2-hydroxy-3,4-dimethoxyphenyl)-1,3-propanedione 
• 460744-02-9 3-chloro-2-(3,4-dimethoxyphenyl)-7,8-dimethoxy-4H-chromen-4-one 
• 460744-06-3 2-(3,4-dimethoxyphenyl)-3-fluoro-7,8-dimethoxy-4H-chromen-4-one 
• 460744-04-1 3-cyano-2-(3,4-dimethoxyphenyl)-7,8-dimethoxy-4H-chromen-4-one 
• 3440-24-2 3',4',7,8-tetrahydroxyflavone 
• 65548-55-2 3',4',7,8-(OMe)4-flavon 

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.

Catecholic flavonoids acting as telomerase inhibitors

In recent years telomerase has been identified as a new promising target in oncology and consequently new telomerase inhibitors have been intensely explored as anticancer agents. Focused screening of several polyhydroxylated flavonoids has allowed us to i

Substituted benzopyranones as telomerase inhibitors

The present invention relates to benzopyranone derivatives, to methods for treating telomerase-modulated diseases, in particular cancers, with said derivatives, to a process for their preparation, to their use as medicaments and to pharmaceutical compositions comprising them.