Ashish Kumar Tewari

Synthesis, biological evaluation and molecular modeling study of pyrazole derivatives as selective COX-2 inhibitors and anti-inflammatory agents.

A novel series of pyrazole derivatives were synthesized and evaluated in vivo for their anti-inflammatory activity in carrageenan-induced rat paw edema model. Among all compounds, 5a, and 5b showed comparable anti-inflammatory activity to Nimesulide, the standard drug taken for the studies. In silico (docking) studies were carried out to investigate the theoretical binding mode of the compounds to target the cyclooxygenase (COX-2) using Autodock 4.2.

Design, synthesis, docking and anti-inflammatory evaluation of novel series of benzofuran based prodrugs.

Several new benzofuran derivatives were synthesized, via appropriate synthetic route as anti-inflammatory agents. The anti-inflammatory activity of the prepared compounds was evaluated using carrageenan rat model. Among the synthesized compounds, some compounds showed comparable anti-inflammatory activity to nimesulide, the standard drug taken for anti-inflammatory studies. Docking study of the prepared compounds was performed for the study of interaction of molecules with the active site of COX-2. Preliminary biological studies and docking gave an interesting insight, into the validity of employing benzofuran analogues as good anti-inflammatory agent.

Unusual reverse face-to-face stacking in propylene linked pyrazole system: perspective of organic materials

Flexible dimers 1, 2, and 3 of “pyrazole” derivatives linked with propylene spacer are synthesized and conformational stability in solid, solution, and gaseous states is studied through single crystal X-ray diffraction, 2D NOESY ,and DFT, respectively. The folded conformation of compound 2 is stable in all three states and X-ray diffraction evince that molecule is intramolecularly stacked in reverse face-to-face manner. TEM image of compound 2 exhibits rigid hollow nanospikes with high tendency to form agglomerates.

Quantum chemical calculation studies for interactions of antiwear lubricant additives with metal surfaces

Theoretical calculations based on density functional theory (DFT) have been performed to correlate experimentally observed antiwear properties of Schiff base lubricant additives derived from condensation of salicylaldehyde with N-phenylthiosemicarbazide, [(E)-1-(2-hydroxybenzylidene)-4-phenylthiosemicarbazide; H2STC-Ph], N-p-tolylthiosemicarbazide [(E)-1-(2-hydroxybenzylidene)-4-p-tolylthiosemicarbazide; H2STC-p-MePh] and N-(4-chlorophenyl)thiosemicarbazide, [(E)-1-(2-hydroxybenzylidene)-4-(4-chlorophenyl)thiosemicarbazide; H2STC-p-ClPh] with their chemical structure. antiwear properties have been discussed on the basis of the interactions between the additive molecules and the metal surface. In order to compare the antiwear behavior of different additives, various parameters such as frontier molecular orbital energy EHOMO (Energy of Highest Occupied Molecular Orbital), ELUMO (Energy of Lowest Unoccupied Molecular Orbital), the energy gap (ΔE), mutual orbitals’ interactions between additive molecules and metal surface (ΔE1 & ΔE2), global properties (hardness and softness) and the dipole moment have been calculated and correlated with the respective energies of the metal surface. The quantum chemical calculations (QCC) have shown that the wear-reducing behavior of Schiff bases increases with an increase in EHOMO, decrease in ELUMO, decrease in the energy gap between ELUMO and EHOMO and increase in the dipole moment of the additives. The results obtained by quantum chemical calculations are in good agreement with the experimental results.

Cascade synthesis of 2-pyridones using acrylamides and ketones

Microwave assisted non-catalytic condensation of 2-cyanoacetamide with aromatic aldehydes, and enolate mediated Michael-type addition to acrylamide followed by oxidative cyclization, produce 2-pyridones in good to excellent yield. Unsymmetrical ketones produce two regioisomeric enolates, therefore thermodynamic and kinetic products of butan-2-one and pentan-2-one have been isolated and fully characterized.

Synthesis of pyrazole-based 1,5-diaryl compounds as potent anti-inflammatory agents

Series of 1,5-diaryl pyrazole ester derivatives have been synthesized and found to contain potent inhibitory activity against cyclooxygenase-2 (COX-2) enzyme. The article describes synthesis of the target pyrazole analogs and biological assay using Carrageenan induced rat paw for investigation.

Erratum to: 2-Substituted-8-methyl-3,6-dihydroimidazo [4,5-c]pyrazolo[3,4-e]pyridazine as an anti-inflammatory agent

A series of 8-methyl-2-substituted-3,6-dihydroimidazo[4,5-c]pyrazolo[3,4-e]pyridazine compounds have been synthesized in the present investigation utilizing Philips condensation (Philips, J Chem Soc 2393–2399, 1928). The anti-inflammatory activity of the synthesized compounds was evaluated using a carrageenin rat model.

Selective induced polarization through electron transfer in acetone and pyrazole ester derivatives via C–H⋯OC interaction

A set of organic compounds (pyrazole ester derivatives, viz. 5-[3-(substituted)-propoxy]-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid methyl ester and 5-[2-(substituted)-ethoxy]-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid methyl ester) was synthesized and their affinity and stability towards the acetone molecule were tested by NMR. Further, the host–guest complex formed has been studied by cyclic voltammetric titration. Interestingly, the acetone molecule selectively bound to the methyl group of the pyrazole moiety and stabilized the system. These findings are also supported by quantum chemical calculations using the DFT/B-LYP/TZVPP method. Apart from hydrogen bonding, an important role in stabilizing the complex is also played by the C–H⋯π interaction governed by dispersion energy. The study proves that a methyl-substituted pyrazol ester can act as a receptor for acetone.

CCSO nano catalyzed solid phase synthesis of 3-oxo-5,6-disubstituted-2,3-dihydropyridazine-4-carbonitrile

Co-doped Ce0.94Ca0.05Sr0.01O1.94 (CCSO) nano particles have been successfully synthesized by an auto-combustion method and were characterized by XRD, TEM and AFM analyses. The catalytic activity of the nano-catalyst is evaluated by the synthesis of substituted pyridazines from substituted benzil and cyano acetylhydrazide, which have great biological and pharmaceutical interest. Thus, a highly economically efficient one-pot solvent free synthesis of pyridazine was developed, which is promoted by the CCSO nano catalyst. The benefits of the reaction are its very short time (2–4 min) and high yields (90–95%). The method offers a highly convergent, inexpensive, and functionality-tolerable procedure for rapid access to important pyridazine compounds in good yields.

Face-to-face stacking in sulfonamide based bis-ethylene bridged heteroaromatic dimers

Four sulfonamide based bis-ethylene bridged heteroaromatic dimers were synthesized for analysis of their structural and conformational properties. Interestingly, all models showed intramolecular offset face-to-face stacking between the tosyl group and heteroaromatic system in their solid state conformations. 1H NMR of the solutions revealed that the conformations were not far off from the solid state stacked geometry. However, gaseous state optimizations of different conformers divulged that the crystal structures were the lowest energy conformers.