4225-35-8

Upstream product

• 103040-51-3 2-chloro-1-(2-hydroxy-4,6-dimethoxyphenyl)ethanone 
• 3260-49-9 4,6-dihydroxybenzofuran-3(2H)-one 
• 77-78-1 dimethyl sulfate 
• 74-88-4 methyl iodide 
• 110865-03-7 2-chloro-1-(2,4,6-trihydroxyphenyl)ethan-1-one 
• 108-73-6 3,5-dihydroxyphenol 
• 18064-88-5 2-bromo-1-(2-hydroxy-4,6-dimethoxyphenyl)ethanone 
• 500-99-2 3,5-dimethoxyphenol 
• 107-14-2 chloroacetonitrile 
• 19728-23-5 2-(3,5-dimethoxyphenoxy)acetic acid 
• 553-86-6 benzofuran-2(3H)-one 
• 28520-50-5 2,4-Diacetoxy-6-methylbenzoesaeureethylester 
• 2524-37-0 ethyl orselinate 
• 91570-58-0 5,7-diacetoxyphthalide 

Downstream Products

• 57060-61-4 2-benzylidene-4,6-dimethoxycoumaran-3-one 
• 10493-04-6 2-(4'-methoxybenzylidene)-4,6-dimethoxycoumaran-3-one 
• 23053-69-2 (Z)-2-(3,4-dimethoxybenzylidene)-4,6-dimethoxybenzofuran-3(2H)-one 
• 350982-87-5 (2Z)-2-(4-fluorobenzylidene)-4,6-dimethoxy-1-benzofuran-3(2H)-one 
• 350982-88-6 (2Z)-2-(4-chlorobenzylidene)-4,6-dimethoxy-1-benzofuran-3(2H)-one 
• 350982-89-7 (Z)-2-(4-bromobenzylidene)-4,6-dimethoxybenzofuran-3(2H)-one 
• 479667-52-2 (Z)-4-((4,6-dimethoxy-3-oxobenzofuran-2(3H)ylidene)methyl)benzonitrile 
• 480-70-6 aureusidin 
• 1092706-09-6 C₂₂H₂₂O₆ 

Relevant academic research and scientific papers

COMPOUNDS HAVING HEPATIAL DISEASE EFFECTIVE

The invention discloses a compound with a hepatopathy curative effect, and the compound is a compound shown as a general formula (I), an optical isomer or pharmaceutically acceptable salt thereof, canbe applied to treatment or prevention of hepatopathy, particularly to drugs for treating or preventing fatty liver, liver fibrosis or liver cirrhosis, and has a good application prospect.

Aurone derivatives as promising antibacterial agents against resistant Gram-positive pathogens

A set of variously substituted aurones was synthesized and evaluated against Methicillin-Resistant S. aureus (MRSA) and P. aeruginosa. Several analogues were found active against MRSA, but no effect was recorded against P. aeruginosa. Compounds 27, 30 and 33 showed low cytotoxicity, and were tested against a full range of bacterial (Gram-positive and Gram-negative) and fungal species, including resistant strains. These aurones displayed a selective inhibition of Gram-positive bacteria with excellent Therapeutic Index values, while showing no significant action on several Gram-negative strains, H. pylori and V. alginolyticus being the only susceptible strains among the Gram-negative bacteria tested. A permeabilization assay showed that the antibacterial activity of at least some of the aurones could be linked to alterations of the bacterial membrane. Overall, this study endorses the use of the aurone scaffold for the development of new potent and selective antibacterial agents.

Synthesis of structurally diverse biflavonoids

Synthetic biflavonoids are associated with interesting biological activities, yet they remain poorly explored within drug discovery. Recent years have witnessed a growing interest in synthetic approaches that can provide access to structurally novel biflavonoids so that the biological usefulness of this compound class can be more fully investigated. Herein, we report upon the exploration of strategies based around Suzuki-Miyaura cross-coupling and alcohol methylenation for the synthesis of two classes of biflavonoids: (i) rare ‘hybrid’ derivatives containing flavonoid monomers belonging to different subclasses, and (ii) homodimeric compounds in which the two flavonoid monomers are linked by a methylenedioxy group. Application of these strategies enabled the preparation of a structurally diverse collection of novel biflavonoids from readily-available starting materials, thereby facilitating the probing of uncharted regions of biologically interesting chemical space.

New pseudodimeric aurones as palm pocket inhibitors of Hepatitis C virus RNA-dependent RNA polymerase

The NS5B RNA-dependent RNA polymerase (RdRp) is a key enzyme for Hepatitis C Virus (HCV) replication. In addition to the catalytic site, this enzyme is characterized by the presence of at least four allosteric pockets making it an interesting target for development of inhibitors as potential anti-HCV drugs. Based on a previous study showing the potential of the naturally occurring aurones as inhibitors of NS5B, we pursued our efforts to focus on pseudodimeric aurones that have never been investigated so far. Hence, 14 original compounds characterized by the presence of a spacer between the benzofuranone moieties were synthesized and investigated as HCV RdRp inhibitors by means of an in vitro assay. The most active inhibitor, pseudodimeric aurone 4, induced high inhibition activity (IC50 Combining double low line 1.3 1/4M). Mutagenic and molecular modeling studies reveal that the binding site for the most active derivatives probably is the palm pocket I instead of the thumb pocket I as for the monomeric derivatives.

Synthesis and evaluation of 4-hydroxyl aurone derivatives as multifunctional agents for the treatment of Alzheimer's disease

A series of 4-hydroxyl aurone derivatives were designed synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. The results demonstrated that most of the derivatives exhibited good multifunctional properties. Among them, compound 14e displayed good inhibitory activities of self- and Cu2+-induced Aβ1-42 aggregation with 99.2% and 84.0% at 25 μM, respectively, and high antioxidant activity with a value 1.90-fold of Trolox. In addition, 14e also showed remarkable inhibitory activities of both monoamine oxidase A and B with IC50 values of 0.271 μM and 0.393 μM, respectively. However the 6-methoxyl aurones 15a-c revealed excellent selectivity toward MAO-B. Furthermore, the representative compounds 14e and 15b displayed good metal-chelating abilities and blood-brain barrier (BBB) permeabilities in vitro.

Combinatorial synthesis of structurally diverse triazole-bridged flavonoid dimers and trimers

Flavonoids are a large family of compounds associated with a broad range of biologically useful properties. In recent years, synthetic compounds that contain two flavonoid units linked together have attracted attention in drug discovery and development projects. Numerous flavonoid dimer systems, incorporating a range of monomers attached via different linkers, have been reported to exhibit interesting bioactivities. From a medicinal chemistry perspective, the 1,2,3-triazole ring system has been identified as a particularly attractive linker moiety in dimeric derivatives (owing to several favourable attributes including proven biological relevance and metabolic stability) and triazole-bridged flavonoid dimers possessing anticancer and antimalarial activities have recently been reported. However, there are relatively few examples of libraries of triazole-bridged flavonoid dimers and the diversity of flavonoid subunits present within these is typically limited. Thus, this compound type arguably remains underexplored within drug discovery. Herein, we report a modular strategy for the synthesis of novel and biologically interesting triazole-bridged flavonoid heterodimers and also very rare heterotrimers from readily available starting materials. Application of this strategy has enabled step-efficient and systematic access to a library of structurally diverse compounds of this sort, with a variety of monomer units belonging to six different structural subclasses of flavonoid successfully incorporated.

Discovery of naturally occurring aurones that are potent allosteric inhibitors of hepatitis C virus RNA-dependent RNA polymerase

We have identified naturally occurring 2-benzylidenebenzofuran-3-ones (aurones) as new templates for non-nucleoside hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) inhibitors. The aurone target site, identified by site-directed mutagenesis, is located in thumb pocket I of HCV RdRp. The RdRp inhibitory activity of 42 aurones was rationally explored in an enzyme assay. Molecular docking studies were used to determine how aurones bind to HCV RdRp and to predict their range of inhibitory activity. Seven aurone derivatives were found to have potent inhibitory effects on HCV RdRp, with IC50 below 5 μM and excellent selectivity index (inhibition activity versus cellular cytotoxicity). The most active aurone analogue was (Z)-2-((1-butyl-1H-indol-3-yl)methylene)-4,6-dihydroxybenzofuran-3(2H)-one (compound 51), with an IC50 of 2.2 μM. Their potent RdRp inhibitory activity and their low toxicity make these molecules attractive candidates as direct-acting anti-HCV agents.

Synthesis and biological evaluation of a novel series of 2,2-bisaminomethylated aurone analogues as anti-inflammatory and antimicrobial agents

This is the first report on aurones as a new class of drugs with anti-inflammatory and antimicrobial agents. A series of 2,2-bisaminomethylated aurone analogues (4a-j) were synthesized by Mannich reaction from 1,3,5-trimethoxybenzene in three steps. The structures of the newly synthesized compounds were confirmed by IR, 1H NMR and mass spectral analysis. All the synthesized compounds were screened against the pro-inflammatory cytokines (TNF-α, IL-6) and antimicrobial (antibacterial and antifungal) activity. Compounds 4a, 4b, 4c, 4d, and 4e showed promising results against IL-6 at 10 mM concentration (74-100%). Compounds 4a, 4b and 4c were found to be active against TNF-α (76-100%) at 10 μM. Interestingly, all compounds have shown good antimicrobial activity. Compounds 4d, 4e and 4f showed excellent antimicrobial activity as compared with standard drugs.

3-SUBSTITUTED-1H-INDOLE, 3-SUBSTITUTED-1H-PYRROLO[2,3-B]PYRIDINE AND 3-SUBSTITUTED-1H-PYRROLO[3,2-B]PYRIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES

The invention relates to 3-substituted-1H-indole, 3-substituted-1H-pyrrolo[2,3-b]pyridine, and 3-substituted-1H-pyrrolo[3,2-b]pyridine compounds of the Formula (I): or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.

Functionalized aurones as inducers of NAD(P)H:quinone oxidoreductase 1 that activate AhR/XRE and Nrf2/ARE signaling pathways: Synthesis, evaluation and SAR

The chemopreventive potential of functionalized aurones and related compounds as inducers of NAD(P)H:quinone oxidoreductase 1 (NQO1, EC 1.6.99.2) are described. Several 4,6-dimethoxy and 5-hydroxyaurones induced NQO1 activity of Hepa1c1c7 cells by 2-fold at submicromolar concentrations, making these the most potent inducers to be identified from this class. Mechanistically, induction of NQO1 was mediated by the activation of AhR/XRE and Nrf2/ARE pathways, indicating that aurones may be mixed activators of NQO1 induction or agents capable of exploiting the proposed cross-talk between the AhR and Nrf2 gene batteries. QSAR analysis by partial least squares projection to latent structures (PLS) identified size parameters, in particular those associated with non-polar surface areas, as an important determinant of induction activity. These were largely determined by the substitution on rings A and B. A stereoelectronic role for the exocyclic double bond as reflected in the E LUMO term was also identified. The electrophilicity of the double bond or its effect on the conformation of the target compound are possible key features for induction activity.