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Structure-based design of a novel, potent, and selective inhibitor for MMP-13 utilizing NMR spectroscopy and computer-aided molecular design

The high-resolution NMR solution structure of the catalytic fragment of human collagenase-3 (MMP-13) was used as a starting point for structure-based design of selective inhibitors for MMP-13. The major structural difference observed between the MMP structures is the relative size and shape of the S1′ pocket where this pocket is significantly longer for MMP-13, nearly reaching the surface of the protein. On the basis of the extended nature of the MMP-13 S1′ pocket an inhibitor potent and selective for MMP-13 was designed from an initial high throughput screening (HTS) lead. CL-82198 was identified as a weak (10 muM) inhibitor against MMP-13 while demonstrating no activity against MMP-1, MMP-9, or the related enzyme TACE. The drug-like properties of CL-82198 made it an ideal candidate for optimization of enzyme potency and selectivity. On the basis of NMR binding studies, it was shown that inhibitor CL-82198 bound within the entire S1′ pocket of MMP-13 which is the basis of its selectivity against MMP-1, MMP-9, and TACE. A strategy utilizing this information was devised for designing new inhibitors that showed enhanced selectivity toward MMP-13. Our design strategy combined the critical selectivity features of CL-82198 with the known potency features of a nonspecific MMP inhibitor (WAY-152177) to generate a potent and selective MMP-13 inhibitor (WAY-170523). WAY-170523 has an IC50 of 17 nM for MMP-13 and showed >5800-, 56-, and >500-fold selectivity against MMP-1, MMP-9, and TACE, respectively.

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Benzofuran – Wikipedia,
Benzofuran | C8H1765O – PubChem

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Palladium-Catalyzed C?H Functionalization of Phenyl 2-Pyridylsulfonates

An efficient palladium(II)-catalyzed intermolecular direct ortho-alkenylation and acetoxylation of phenols has been developed. The reaction proceeded via a seven-membered cyclopalladated intermediate and showed complete regio- and diastereoselectivity. The approach also provided an efficient route for the synthesis of coumarins and benzofurans.

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Benzofuran – Wikipedia,
Benzofuran | C8H1874O – PubChem

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Sordaricin antifungal agents

Compounds based on sordaricin were prepared via organometallic addition onto a fully protected sordaricin aldehyde. The fungal growth inhibition profiles for these compounds were established and the results are presented here. The synthesis of homologated sordaricin as well as ether and ester derivatives is presented, and structural rearrangement products upon oxidation. These compounds were evaluated as agents to inhibit fungal growth.

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Benzofuran – Wikipedia,
Benzofuran | C8H1935O – PubChem

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The proportionality constant is the rate constant for the particular unimolecular reaction. the reaction rate is directly proportional to the concentration of the reactant. I hope my blog about 496-41-3 is helpful to your research. Synthetic Route of 496-41-3

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A benzofuran -2 – preparation of formic acid method (by machine translation)

A benzofuran – 2 – carboxylic acid, which belongs to the benzofuran – 2 – carboxylic acid technical field. Is to metallic iron porphyrin catalytic oxygen oxidation 2 – methyl benzofuran preparation of benzofuran – 2 – carboxylic acid, which belongs to the field of organic synthesis and green chemistry. The method uses 2 – methyl benzofuran as raw materials, in order to ethanol or ethanol aqueous solution as the solvent, metal porphyrin four (O – chlorophenyl) iron porphyrin as catalyst, oxygen as the oxidizing agent, sodium hydroxide or potassium hydroxide is used as the cocatalyst, for 80 – 130 C reaction under 1 – 4 hours, after the reactant is acidified, filtration, recrystallization to obtain product benzofuran – 2 – carboxylic acid. The method of the invention catalyst the amount of raw material weight 0.02 – 0.05%, less catalyst levels and without the need of separation, clean oxygen as the oxidizing agent, and the pressure is 0.5 – 2.0 mpa, solvent environment friendly, the reaction temperature is lower, the reaction raw materials through a simple separation, but also can be recycled. (by machine translation)

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Benzofuran – Wikipedia,
Benzofuran | C8H1627O – PubChem

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N-quinolinyl alkyl-substituted 1-aryloxy-2-propanolamine and propylamine derivatives possessing class III antiarrhythmic activity

This invention relates to N-heteroalkyl-substituted 1-aryloxy-2-propanolamine and propylamine derivatives possessing anti-arrhythmic activity, to pharmaceutical compositions and to methods for production thereof.

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Benzofuran – Wikipedia,
Benzofuran | C8H1639O – PubChem

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Palladium-catalyzed direct C-H silylation and germanylation of benzamides and carboxamides

A palladium-catalyzed regioselective activation of C(sp2)-H and C(sp3)-H bonds of benzamides and carboxamides, followed by coupling with disilanes to afford organosilanes in moderate to high yields, with the aid of 8-aminoquinoline as a directing group, is reported. Catalytic C(sp 2)-H germanylation of benzamides also proceeds under the same palladium catalysis. The reaction tolerates a wide variety of functional groups and is scalable without yield reduction. The bidentate directing group is readily removed and recovered by the reaction with a hydrazine, with concominant generation of an acyl hydrazide.

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Benzofuran – Wikipedia,
Benzofuran | C8H1841O – PubChem

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Inhibition of FLT3 and PDGFR tyrosine kinase activity by bis(benzo[b]furan-2-yl)methanones

A series of bis(benzo[b]furan-2-yl)methanones was synthesized and tested for inhibition of FLT3 and PDGFR autophosphorylation. Mostly, C-5 substitution leads to PDGFR selectivity, which was strongest in the case of the 5,5?-dimethoxy derivative. The 5,5?-diamino and the 6,6?-dihydroxy compounds are more active at FLT3. At both kinases, the potency of the best inhibitors approaches IC50 values of ca. 0.5 muM. Molecular modeling studies suggest that the bisbenzofuranylmethanones are able to fit into the same binding site as their indolyl analogues which have been suggested to form a bidentate hydrogen bridge with the backbone in the hinge regions. The loss of one H bond by the NH-O exchange might be partially compensated by, for example, the weak interaction of one furanyl oxygen with FLT3 Cys-828.

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Benzofuran – Wikipedia,
Benzofuran | C8H1888O – PubChem

Brief introduction of Benzofuran-2-carboxylic acid

The proportionality constant is the rate constant for the particular unimolecular reaction. the reaction rate is directly proportional to the concentration of the reactant. I hope my blog about 496-41-3 is helpful to your research. Application of 496-41-3

Application of 496-41-3, Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 496-41-3, molcular formula is C9H6O3, introducing its new discovery.

Novel low molecular renin inhibitors which show good oral blood pressure lowering effects in marmosets

A series of low molecular renin inhibitors (molecular weight < 600) were prepared and their biological activities were evaluated. The inhibitors containing indole-2-carbonyl moieties at the P3 position and 2-amino-3,5-anti-diol fragment at the P1-P1' position showed renin inhibitory activities with IC50 of 10-8 M order and good blood pressure lowering effects after oral administration to sodium-depleted marmosets. The proportionality constant is the rate constant for the particular unimolecular reaction. the reaction rate is directly proportional to the concentration of the reactant. I hope my blog about 496-41-3 is helpful to your research. Application of 496-41-3

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Benzofuran – Wikipedia,
Benzofuran | C8H2033O – PubChem

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Synthesis and biological evaluation of novel shikonin-benzo[b]furan derivatives as tubulin polymerization inhibitors targeting the colchicine binding site

A novel series of shikonin-benzo[b]furan derivatives were designed and synthesized as tubulin polymerization inhibitors, and their biological activities were evaluated. Most compounds revealed the comparable anti-proliferation activities against the cancer cell lines to that of shikonin and simultaneously low cytotoxicity to non-cancer cells. Among them, compound 6c displayed powerful anti-cancer activity with the IC50 value of 0.18 muM against HT29 cells, which was significantly better than that of the reference drugs shikonin and CA-4. What’s more, 6c could inhibit tubulin polymerization and compete with [3H] colchicine in binding to tubulin. Further biological studies depicted that 6c can induce cell apoptosis and cell mitochondria depolarize, regulate the expression of apoptosis related proteins in HT29 cells. Besides, 6c actuated the HT29 cell cycle arrest at G2/M phase, and influenced the expression of the cell-cycle related protein. Moreover, 6c displayed potent inhibition on cell migration and tube formation that contributes to the antiangiogenesis. These results prompt us to consider 6c as a potential tubulin polymerization inhibitor and is worthy for further study.

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Benzofuran – Wikipedia,
Benzofuran | C8H1850O – PubChem

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Switchable Selectivity in the Pd-Catalyzed Alkylative Cross-Coupling of Esters

The Pd-catalyzed cross-coupling of phenyl esters and alkyl boranes is disclosed. Two reaction modes are rendered accessible in a selective fashion by interchange of the catalyst. With a Pd-NHC system, alkyl ketones can be prepared in good yields via a Suzuki-Miyaura reaction proceeding by activation of the C(acyl)-O bond. Use of a Pd-dcype catalyst enables alkylated arenes to be synthesized by a modified pathway with extrusion of CO. Applications of this divergent coupling strategy and the origin of the switchable selectivity are discussed.

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Reference£º
Benzofuran – Wikipedia,
Benzofuran | C8H1896O – PubChem