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Design, synthesis, and biological evaluation of N-carboxyphenylpyrrole derivatives as potent HIV fusion inhibitors targeting gp41

On the basis of the structures of small-molecule hits targeting the HIV-1 gp41, N-(4-carboxy-3-hydroxy)phenyl-2,5-dimethylpyrrole (2, NB-2), and N-(3-carboxy-4-chloro)phenylpyrrole (A1, NB-64), 42 N-carboxyphenylpyrrole derivatives in two categories (A and B series) were designed and synthesized. We found that 11 compounds exhibited promising anti-HIV-1 activity at micromolar level and their antiviral activity was correlated with their inhibitory activity on gp41 six-helix bundle formation, suggesting that these compounds block HIV fusion and entry by disrupting gp41 core formation. The structure-activity relationship and molecular docking analysis revealed that the carboxyl group could interact with either Arg579 or Lys574 to form salt bridges and two methyl groups on the pyrrole ring were favorable for interaction with the residues in gp41 pocket. The most active compound, N-(3-carboxy-4-hydroxy)phenyl-2,5-dimethylpyrrole (A12), partially occupied the deep hydrophobic pocket, suggesting that enlarging the molecular size of A12 could improve its binding affinity and anti-HIV-1 activity for further development as a small-molecule HIV fusion and entry inhibitor.

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Organotin complexes containing carboxylate ligands with maleimide and naphthalimide derived partial structures: TrxR inhibition, cytotoxicity and activity in resistant cancer cells

Di-n-butyltin(IV) carboxylate and tri-n-butyltin(IV) carboxylate derivatives have demonstrated strong cytotoxic effects in different types of tumor cells. Complexes with carboxylate ligands that contain maleimide and naphthalimide derived partial structures were synthesized, characterized and investigated for inhibition of the tumor-relevant enzyme thioredoxin reductase and antiproliferative effects in cancer cells. The complexes were moderate inhibitors of thioredoxin reductase with activities in the micromolar range and triggered strong cytotoxic effects in MCF-7 breast cancer and HT-29 colon carcinoma cells. Interestingly, selected complexes were highly active in vincristine and daunorubicin resistant Nalm-6 cells.

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Design and synthesis of a novel DNA-encoded chemical library using Diels-Alder cycloadditions

DNA-encoded chemical libraries are increasingly being employed for the identification of binding molecules to protein targets of pharmaceutical relevance. Here, we describe the synthesis and characterization of a DNA-encoded chemical library, consisting of 4000 compounds generated by Diels-Alder cycloaddition reactions. The compounds were encoded with unique DNA fragments which were generated through a stepwise assembly process and serve as amplifiable bar codes for the identification and relative quantification of library members.

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Ex vivo anticholinesterase activity of benzoic acid derivatives.

p-Aminobenzoic acid (p-ABA) derivatives were evaluated as acetylcholinesterase inhibitors (AChEIs). Finding a correlation between AChE activity with the partition coefficient (log P) and the highest occupied molecular orbital (HOMO) energy of the compounds.

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Synthesis and antibacterial activity of new 2,5-diaryl-3-styryl-4H,2,3,3a, 5,6,6a-hexahydropyrrolo[3,4-d]isoxazole-4,6-diones

The synthesis of some biologically interesting pyrrolo-isoxazolidine derivatives has been accomplished by the 1,3-dipolar cycloaddition reaction of substituted open chain conjugated azomethine N-oxides 1 with substituted N-aryl maleimides 2 leading to the formation of new stereoisomeric 2,5-diaryl-3-styryl- 4H,2,3,3a,5,6,6a-hexahydropyrrolo[3,4-d]isoxazole-4,6-dione derivatives 3 in excellent yields. These stereoisomers have been characterized as cis-3A and trans-3B on the basis of their 1H-NMR spectral measurements. The synthesized compounds have been screened for their antibacterial activities and have been found to be active against the bacteria Escherichia coli and Pseudomonas aeruginosa up to a significant extent.

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Bio-based thermosetting resins composed of aliphatic polyol-derived polymaleimides and allyleugenol

Bio-based bismaleimide (2MPD), trismaleimide (3MGC) and tetramaleimide (4MDG) were synthesized by reactions of 4-isocyanatophenylmaleimide with 1,3-propanediol, glycerol and alpha,alpha?-diglycerol, respectively. Although 2MPD did not melt until the temperature where thermal decomposition starts, 3MGC and 4MDG exhibited broad melting temperatures with onset points at 165 C and 124 C, respectively. 3MGC and 4MDG were homogeneously prepolymerized at 170 C with 2,4-diallyl-6-methoxyphenol (rAEG) which was prepared by the Claisen rearrangement of allyl-etherified eugenol (AEG). The prepolymers were compression-molded at 250 C to produce cured rAEG/3MGC (A3Mxy) and rAEG/4MDG (A4Mxy) with the allyl/maleimide ratio of x/y = 1/1, 1/2 or 1/3. The FT-IR analysis revealed that the ene reaction of allyl and maleimide groups and subsequent addition copolymerization occurred for the cured resins. The thermal and mechanical properties of the cured resins were compared with those of the cured rAEG/4,4?-bismaleimidodiphenylmethane (BMI) (ABMxy) with the same allyl/maleimide ratio. A3M13 and A4M13 showed no inflection point of thermal expansion due to glass transition until 300 C, which is a little lower than the thermo-degradation temperature. Flexural strengths and flexural strains at break for A3Ms and A4Ms increased with the polymaleimide contents, and those of A3M13 and A4M13 were much higher than those of ABM13.

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Binuclear platinum(II) complexes based on a new bis-bidentate 3,6-di(thien-2-yl)pyridazine skeleton, a novel type of deep-red phosphorescent emitters: Synthesis and nonempirical calculations

Three novel template bis-bidentate ligands based on {3,6-di(thien-2-yl)pyridazine} skeleton and four binuclear Pt(II) complexes containing these metalating templates were synthesized and characterized including photophysical study of two emissive compounds. These complexes display phosphorescence from triplet excited state localized primarily at the thienyl-pyridazine aromatic system, the emission bands being unusually strong shifted (ca. 100 nm/4380 cm?1) to the NIR region compared to analogous phenyl-pyridazine complexes. The absorption and emission characteristics of the complexes were analyzed by using DFT and TD DFT calculations. The results of calculations confirm that emission originates from a mixture of 3LC, 3MLCT, 3LLCT with major contribution of the former excited state and show reasonable agreement with the experimental data.

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Discovery of 4-(2,5-Dioxo-2,5-dihydro-pyrrol-1-yl)-benzoicacid

Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data. Computed Properties of C11H7NO4, If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 17057-04-4, in my other articles.

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4-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoic acid: X-ray and DFT-calculated structure

In the title compound, C11H7NO4, there is a dihedral angle of 45.80 (7) between the planes of the benzene and maleimide rings. The presence of O – H…O hydrogen bonding and weak C – H…O inter-actions allows the formation of R33(19) edge-connected rings parallel to the (010) plane. Structural, spectroscopic and theoretical studies were carried out. Density functional theory (DFT) optimized structures at the B3LYP/6-311 G(d,p) and 6-31++G(d,p) levels are compared with the experimentally determined mol-ecular structure in the solid state. Additional IR and UV theoretical studies allowed the presence of functional groups and the transition bands of the system to be identified.

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Balanced chemical reaction does not necessarily reveal either the individual elementary reactions by which a reaction occurs or its rate law.Electric Literature of 17057-04-4. In my other articles, you can also check out more blogs about 17057-04-4

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Effect of chemical structure on the crosslinking behavior of bismaleimides: Rheological study

The effect of molecular structure on the cure characteristics of bismaleimides (BMIs) was investigated by rheological measurements. BMI resins of different chemical structures were used, prepared from diglycidyl ether of bisphenol A and N-(3-carboxy phenyl) maleimide or N-(4-carboxy phenyl) maleimide. Temperature dependence of the rheological data was correlated to the Arrhenius equation, from which the activation energy of crosslinking was calculated.Upon heating in dynamic curing, viscosity passed through a minimum then sharply increased due to increasing amount of the crosslinking reaction. The temperature at minimum viscosity increased as the chain length became longer. After passing the minimum point, viscosity increased much faster for meta BMIs (3BE1, 3BE2) than para BMIs, however, the difference in the chain length did not show any appreciable difference in the viscosity increase rate (deta*/dT). Nonetheless, the final viscosity was lower for longer chains, because their crosslinking density would be lower.In isothermal curing, the final crosslinking density was expected to increase with temperature, which was shown via the increase in the final viscosity. The gelation time decreased with temperature, and the activation energy of the crosslinking reaction was obtained. Using the reaction kinetics parameters obtained from dynamic scanning calorimeter and Arrhenius type equation, the viscosity change during the isothermal curing was simulated and compared with the measurements.

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AMINOBENZOIC ACID DERIVATIVES FOR USE AS ANTI-INFLAMMATORY AGENTS, ANTI-METASTATIC AGENTS AND/OR ANTICANCER AGENTS

There are provided compounds of formula (I) in which R2, R2, R3, R4 and Q can represent various different possibilities. These compounds can be useful as anticancer agents as well as anti-inflammatory agents, anti-proliferative agents and/or anti-metastatic agents.

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