1484-73-7

Usage

InChI:InChI=1/C12H12O3/c1-3-8-5-9-7(2)4-12(14)15-11(9)6-10(8)13/h4-6,13H,3H2,1-2H3

Upstream product

• 2896-60-8 4-ethyl-1,3-benzenediol 
• 141-97-9 ethyl acetoacetate 
• 94739-92-1 7-furoyloxy-6-ethyl-4-methylcoumarin 
• 7664-93-9 sulfuric acid 
• 60965-25-5 5'-bromo-2',4'-dihydroxyacetophenone 
• 19672-02-7 5-ethyl-2-methoxyphenyl 
• 6626-15-9 4-Bromoresorcinol 
• 552-41-0 1-(2-hydroxy-4-methoxyphenyl)ethanone 
• 16555-98-9 6-acetyl-7-hydroxy-4-methylcoumarin 
• 109159-90-2 6-ethyl-7-methoxy-4-methylcoumarin 

Downstream Products

• 109103-15-3 7-acetoxy-6-ethyl-4-methylcoumarin 
• 108988-24-5 6-ethyl-7-hydroxy-4-methyl-2-oxo-2H-chromene-3,8-disulfonic acid 
• 114946-62-2 6-ethyl-7-benzoyloxy-4-methyl-8-propionyl-coumarin 
• 257621-37-7 5'-ethyl-2',6'-dihydroxyacetophenone 2'-O-(2,3,4,6-O-tetraacetyl)-β-D-glucopyranoside 
• 54337-59-6 3'-ethyl-2',6'-dihydroxyacetophenone 
• 94964-98-4 9-benzyl-6-ethyl-4-methyl-9,10-dihydro-8H-chromeno[8,7-e][1,3]oxazin-2-one 
• 88827-61-6 6-ethyl-4-methyl-9-phenyl-9,10-dihydro-8H-chromeno[8,7-e][1,3]oxazin-2-one 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of novel trimethylangelicin analogues targeting nuclear factor kB (NF-kB)

A series of trimethylangelicin (TMA) derivatives were designed and synthesized to overcome the unwanted effects of TMA, promising agent for treatment of inflammation-related diseases and other pathologies, such as cystic fibrosis. The new generation TMA analogues bore hindered substituents at the 4 position in order to minimize or avoid the photoreactions with DNA. Among them, the 4-isopropyl-6-ethyl derivative 23 exhibited TMA-like inhibitory activity on NF-κB/DNA interactions but it proved unable to photoreact with pyrimidine bases of DNA, nor to induce any other DNA damage. The isopropyl analogue 23 was proven to lack mutagenicity when assayed through Ames test and exhibited no anti-proliferative activity on cystic fibrosis IB3-1 cells, displaying at the same time inhibition of the TNF-α induced release of the NF-κB regulated PDGF-B chain, IL-10, IL-15, IL-17 and IFN-γ. Therefore compound 23 deserves further assay to determine its anti-inflammatory properties, since it lacks photoreaction properties and mutagenicity-related side effects.

Synthesis and structure-activity relationship of coumarins as potent Mcl-1 inhibitors for cancer treatment

Myeloid cell leukemia-1 (Mcl-1) is a validated and attractive target for cancer therapy. Over-expression of Mcl-1 in many cancers allows cancer cells to evade apoptosis and contributes to their resistance to current chemotherapeutics. In this study, more than thirty coumarin derivatives with different substituents were designed and synthesized, and their Mcl-1 inhibitory activities evaluated using a fluorescence polarization-based binding assay. The results showed that the catechol group was a key constituent for Mcl-1 inhibitory activity of the coumarins, and methylation of the catechol group led to decreased inhibitory activity. The introduction of a hydrophobic electron-withdrawing group at the C-4 position of 6,7-dihydroxycoumarin, enhanced Mcl-1 inhibitory capacity, and a hydrophilic group in this position was unbeneficial to the inhibitory potency. In addition, the introduction of a nitrogen-containing group to the C-5 or C-8 position, which allowed an intramolecular hydrogen bond, was also unfavorable for Mcl-1 inhibition. Among all coumarins tested, 4-trifluoromethyl-6,7-dihydroxycoumarin (Cpd 4) displayed the most potent inhibitory activity towards Mcl-1 (Ki = 0.21 ± 0.02 μM, IC50 = 1.21 ± 0.56 μM, respectively), for which the beneficial effect on taxol resistance was also validated in A549 cells. A strong interaction between Cpd 4 and Mcl-1 in docking simulations further supported the observed potent Mcl-1 inhibition ability of Cpd 4. 3D-QSAR analysis of all tested coumarin derivatives further provides new insights into the relationships linking the inhibitory effects on Mcl-1 and the steric-electrostatic properties of coumarins. These findings could be of great value for medicinal chemists for the design and development of more potent Mcl-1 inhibitors for biomedical applications.

Establishing a flow process to coumarin-8-carbaldehydes as important synthetic scaffolds

Despite their usefulness as fluorophores and synthetic precursors, efficient and reliable routes to coumarin-8-carbaldehydes are lacking. We describe here a high-yielding continuous flow synthesis that requires no manual intermediate purification or work-up, giving access to multigram quantities of the aldehyde product. Aldehyde on tap: Despite their usefulness as fluorophores and synthetic precursors, efficient and reliable routes to coumarin-8- carbaldehydes are lacking. A high-yielding continuous flow synthesis that requires no manual intermediate purification or work-up is described, giving access to multigram quantities of aldehyde product (see scheme). Copyright

Skeletal diversity construction via a branching synthetic strategy

A branching synthetic strategy was used to efficiently generate structurally diverse scaffolds, which span a broad area of chemical descriptor space, and their biological activity against MRSA was demonstrated. The Royal Society of Chemistry 2006.

Na+-glucose cotransporter (SGLT) inhibitors as antidiabetic agents. 4. Synthesis and pharmacological properties of 4'- dehydroxyphlorizin derivatives substituted on the B ring

In our studies of Na+-glucose cotransporter (SGLT) inhibitors as antidiabetic agents, a series of novel 4'- dehydroxyphlorizin derivatives substituted on the B ring was prepared and their effects on urinary glucose excretion were evaluated in rats. Introduction of only a small alkyl group at the 4'-position increased the activity, and 3-(benzo[b]furan-5- yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-β-D- glucopyranoside (4) showed the most potent effect. To overcome hydrolysis of compound 4 by β-glucosidase in the digestive tract, the OH groups on the glucose moiety of compound 4 were modified. Three prodrugs (5, 42, and 55) were more potent than the parent compound 4 by oral administration, and finally 3- (benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O- (6-O-methoxycarbonyl-β-D-glucopyranoside) (5) was selected as a new promising candidate. Compound 5 was metabolized mainly by liver esterase to the active form (4), which was about 10 times more potent than 5 in inhibiting SGLT. In oral glucose tolerance test in db/db mice, compound 5 dose-dependently suppressed the elevation of glucose levels. Single administration of 5 reduced hyperglycemia concurrently with increase of glucose excretion into urine in diabetic KK-A(y) mice. Furthermore, compound 5 suppressed the elevation of blood glucose levels but did not lower it below the normal level even in fasted conditions in KK- A(y) mice. Additionally, long-term treatment with 5 dose- dependently reduced hyperglycemia and HbA1c in KK-A(y) mice. These pharmacological data strongly suggest that compound 5 has a therapeutic potential in the treatment of NIDDM.

CONDENSATION OF ETHYL ACETOACETATE AND ETHYL BENZOYLACETATE WITH 4-ALKYLRESORCINOLS IN THE PRESENCE OF BF3 ETHER COMPLEX

The reactions of ethyl acetoacetate and ethyl benzoylacetate with 4-alkylresorcinols catalyzed by BF3 ether complex, give new 6-alkyl-7-hydroxy-4-methyl- and 6-alkyl-7-hydroxy-4-phenyl-coumarins.A mechanism of coumarin formation is suggested.

Photo-induced Reactions: Part IV-Studies on Photo Fries Migration of Some Coumarins

Photo-Fries migration as an alternative route to acylcoumarins has been investigated. 7-Acetoxy- and 7-furoyloxy-coumarins give 6-acylcoumarins as the major products in contrast to Lewis acid mediated Fries migration where 8-acyl derivatives are the major products.The benzoates on the other hand give 6- and 8-acylcoumarins in equal proportions.The method is not suitable for the preparation of long chain unsaturated acyl derivatives of coumarins because in such cases photolytic deesterification is the main route.