Browsing by Author "Ashish Kumar Tewari"

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2-Substituted-8-methyl-3,6-dihydroimidazo[4,5-c]pyrazolo[3,4-e] pyridazine as an anti-inflammatory agent
(2011) Ashish Kumar Tewari; Rashmi Dubey; Anil Mishra
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. © Springer Science+Business Media, LLC 2010.
A Case of Folding Pattern in Flexible Tripodal of N-Substituted Bisethylenamine Bridged Pyridazinone Dimers
(Wiley-Blackwell, 2017) Ranjeet Kumar; Archana Gaurav; Shiv Pal; Ashish Kumar Tewari
Present manuscript reports three tripodal molecules for their special structural and conformational properties. Interestingly, X-ray structure revealed that all these molecules adopt folded conformation in solid state. Further, these molecules are flexible due to linker, may exist in various conformations, the studies have been carried out with different conformers through theoretical calculation in gaseous state. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
A new polymorph of 4,4′-(ethyl-enedi-oxy)dibenzaldehyde
(2007) Ashish Kumar Tewari; Ved Prakash Singh; Carmen Puerta; Pedro Valerga
The crystal structure of a new crystalline form of 4,4′-(ethyl-enedi- oxy)dibenzaldehyde, C16H14O4, has been determined in the space group Cc using low-temperature X-ray diffraction data. The two phenyl rings have a dihedral angle of 76.03 (6)°, in contrast to their near-coplanarity in the previously reported polymorph. © International Union of Crystallography 2007.
An Experimental and Theoretical Study of the Conformational Stability of Triazinone Fleximers: Quantitative Analysis for Intermolecular Interactions
(John Wiley and Sons Inc, 2023) Akhilesh Kumar; Praveen Singh; Ranjeet Kumar; Priyanka Yadav; Amit Jaiswal; Ashish Kumar Tewari
Synthesis and characterization of triazinone based propylene linked phthalimide and benzimidazole have been carried out for conformational analysis and the study of their quantitative intermolecular interactions. The conformational analyses have been calculated by X-ray crystallography in the solid state and theoretical calculations in the gaseous state. From the crystal structure and theoretical calculations we have found that all compounds are stable in the folded conformation. These stable conformations are stabilized by different intra and intermolecular interactions, such as C−H⋯O, C−H⋯N, C−H⋯π and π⋯π. Quantitative intermolecular interactions and interactions energy calculations of both compounds have been carried out by Hirshfeld surface analysis. © 2023 Wiley-VCH GmbH.
Applications of dithioacetals in ester synthesis
(2009) Ashish Kumar Tewari; Priyanka Srivastava
The α-oxoketene dithioacetals are simple synthetic intermediates widely utilized and implicated for the synthesis of a variety of heterocyclic compounds other than alicyclic and aromatic compounds. They act as 1,3-electrophilic three-carbon synthons. The -oxoketene dithioacetal of pyrazolone derivatives can be efficiently converted through a base-catalyzed alcoholysis into the corresponding ester in a single one-step reaction with good yield of pure products. In this article, we summarize recent direct conversion of α-oxoketene dithioacetals to highly desirable esters. The overall process is an example of intramolecular rearrangement of bonds. Characterization and identification of all synthesized compounds were assigned through 1H NMR and mass spectroscopy.
CCSO nano catalyzed solid phase synthesis of 3-oxo-5,6-disubstituted-2,3-dihydropyridazine-4-carbonitrile
(Royal Society of Chemistry, 2014) Praveen Singh; Ranjeet Kumar; Brijesh Kumar Yadav; Ranjana S. Khanna; Ashish Kumar Tewari
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. This journal is © the Partner Organisations 2014.
Click inspired novel pyrazole-triazole-persulfonimide & pyrazole-triazole-aryl derivatives; Design, synthesis, DPP-4 inhibitor with potential anti-diabetic agents
(Academic Press Inc., 2022) Manisha Nidhar; Shaziya Khanam; Priyanka Sonker; Priya Gupta; Archisman Mahapatra; Swaraj Patil; Brijesh Kumar Yadav; Rahul Kumar Singh; Ashish Kumar Tewari
This work presented the first report on designing, synthesizing of novel pyrazole-triazole-persulfonimide (7a-i) and pyrazole-triazole-aryl derivatives (8a-j) via click reaction using CuI catalyst and evaluated for their anti-diabetic activity and DPP-4 inhibitory effect. Click reactions went smoothly with CuI catalyst in the presence of tridentate chelating ligands and produced copper-free target pyrazole-triazole-persulfonimide analogues in excellent yield at RT. The designed compounds were docked against DPP-4 enzyme and showed excellent interaction with active amino acids residue. Further, all novel pyrazole-triazole-persulfonimide and pyrazole-triazole derivatives were subjected to enzyme-based in vitro DPP-4 inhibitory activity. Based on the SAR study DPP-4 inhibitory capacity compounds 7f (9.52 nM) and 8h (4.54 nM) possessed the significant inhibition of DPP-4. Finally compounds 7f and 8h were evaluated for their in vivo anti-diabetic activity using STZ induced diabetic mice model, and 8h showed a significant diabetic control effect compared to the sitagliptin drug. These studies demonstrated that the novel pyrazole-triazole-persulfonimide and pyrazole-triazole-aryl derivatives might be used as the leading compounds to develop novel DPP-4 inhibitors as potential anti-diabetic agents. © 2022 Elsevier Inc.
Conformation of (-)/(l)-1,3-bis(4,6-dimethyl-1H-nicotinonitril-1-yl)1,3- dithioxypropane stabilized via intra/intermolecular weak interactions
(2011) Rashmi Dubey; Ashish Kumar Tewari; K. Ravikumar; B. Sridhar
In solution state, the stable gauche conformation of 1,3-bis(4,6-dimethyl- 1H-nicotinonitril-1-yl)1,3-dithioxypropane is predicted by CD spectra. Weak interaction present in the molecule makes it flexible, and due to this reason helicity is observed in it. In solid state, the molecular conformation and packing geometry is stabilized via both intra/inter molecular CH•••N, CH•••S and π•••π interactions. © 2011 Springer Science+Business Media, LLC.
Design, synthesis and in-silico & in vitro enzymatic inhibition assays of pyrazole-chalcone derivatives as dual inhibitors of α-amylase & DPP-4 enzyme
(Springer Science and Business Media Deutschland GmbH, 2022) Manisha Nidhar; Priyanka Sonker; Vishal Prasad Sharma; Sanjay Kumar; Ashish Kumar Tewari
A series of pyrazole-chalcone derivatives were designed, synthesized and evaluated for their in vitro α-amylase & DPP-4 inhibitory activity. The structure of the compounds thus prepared was confirmed by analytical, and spectral techniques, 1H-NMR, 13C-NMR and Mass spectroscopy. To preliminarily investigate the molecular targets and to confirm the experimental activity testing for these anti-diabetic compounds, the molecular docking studies were determined, using different target receptors i.e., DPP-4 (PDB: 2OLE), PPARγ (PDB: 5Y2O) & α-amylase enzyme (PDB: 5E0F). The docking study results revealed that pyrazole-chalcone derivatives exhibited better binding interaction to α-amylase enzyme over the DPP-4 enzyme & PPARγ. Depending on in silico experiments the designed compounds were selectively prioritized for synthesis. The synthesized compounds were subjected to enzyme-based in vitro α-amylase, DPP-4 inhibitory, and antioxidant activity. ADMET parameters like HBD, HBA, PSA, cLogP, molecular weight, bioavailability, and drug-likeness further confirmed that the compounds are potential lead compounds for future study. Compounds 4d and 6a exhibited highest activity toward α-amylase enzyme and DPP-4 enzyme. © 2021, Institute of Chemistry, Slovak Academy of Sciences.
Design, synthesis, and molecular modeling of heterodimer and inhibitors of α-amylase as hypoglycemic agents
(Institute for Ionics, 2023) Ved Prakash Singh; Manisha Nidhar; Pratima Yadav; Ranjeet Kumar; Priyanka Sonker; Ashish Kumar Tewari
A series of rosiglitazone-based heterodimers were designed and synthesized, and their α-amylase and antioxidant activity was evaluated. The binding mode of the compounds at the active site of PPARγ and α-amylase enzyme was explored using MolDock docking method. In molecular docking studies against crystal structure of PPARγ (PDB code: 1FM6), compounds 10 and 13 showed interaction with amino acids Arg379, Asp379, Asn385, Ala387, Glu388, Val389, Glu390, and Lys438. Docking results of α-amylase enzyme (PDB code: 5EOF) with compounds 10 and 13 showed excellent interaction with amino acids Ala169, Lys172, Asp173, Tyr174, Val175, Arg176, and Lys178. Depending on the docking score, the designed compounds were selectively prioritized for synthesis. All synthesized compounds were subjected to in vitro α-amylase activity and antioxidant activity. Compounds 10 and 13 were to possess higher potency than acarbose, and most of the compounds showed antioxidant activity. Additionally, the most active compound 10 was evaluated for in vivo anti-diabetic activity. Graphical abstract: [Figure not available: see fulltext.]. © 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Design, synthesis, docking and anti-inflammatory evaluation of novel series of benzofuran based prodrugs
(Elsevier Ltd, 2014) Pratima Yadav; Praveen Singh; Ashish Kumar Tewari
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. © 2014 Elsevier Ltd. All rights reserved.
Design, synthesis, in silico analysis with PPAR-γ receptor and study of non-covalent interactions in unsymmetrical heterocyclic/phenyl fleximer
(Chinese Chemical Society Taiwan, 2021) Ved Prakash Singh; Jayanta Dowarah; Brilliant N. Marak; Ashish Kumar Tewari
This work deals with the design, synthesis, in silico analysis, crystallization, and the interpretation 2-cyano-3-{4-[2-(phthalimid-nyl)-propoxy]-phenyl}-acrylic acid ethyl ester (7). Analog 7 is designed based on rosiglitazone. The quantitative analysis of Compound 7 has been performed through single-crystal X-Ray Diffraction (XRD) and Hirshfeld surface analysis. Fleximer 7 has studied the role of flexibility in non-covalent interactions and binding affinity with PPAR-γ receptors. Both phthalimide ring and phenyl rings are linked with propylene linker. 2-cyano-3-{4-[2-(phthalimid-nyl)-propoxy]-phenyl}-acrylic acid ethyl ester has Z = 8 in the crystal packing and stabilized by intermolecular non-covalent interactions like C-H…O, C-H…N, C-H…л, and л…л, and so forth. © 2020 The Chemical Society Located in Taipei & Wiley-VCH GmbH
Design, Synthesis, in Silico and in Vitro Dipeptidyl Peptidase-4 Activity of Triazole-Based Heterocyclic Compounds
(John Wiley and Sons Inc, 2025) Ranjeet Kumar; Manisha Nidhar; Ashish Kumar Tewari
1,2,3-triazole-based ring connected with pyridazine, triazine, methyl pyrazole, diphenyl pyrazole, and phthalimide moieties through propylene linker has been synthesized for antidiabetic evaluation via click chemistry. The antidiabetic evaluations have been done by molecular docking studies and in-vitro tests against the dipeptidyl peptidase-4 (DPP-4) enzyme. The molecular docking studies have revealed that compounds 22, 23, 29, and 30 showed hydrogen bonds with the DPP-4 enzyme while in-vitro tests have revealed that compound 30 has (IC50 values 12.82 nM), exhibited potent activity compared to the standard drug, sitagliptin (14.8 nM). Among the heterocyclic compounds, phthalimide and pyrazole derivatives were found more potent for DPP-4 inhibitors. © 2024 Wiley-VHCA AG, Zurich, Switzerland.
Designing DPP-4 inhibitors: Synthesis, characterization, in silico & in vitro evaluation, and theoretical calculation of flexible compounds linked via ortho xylyl spacers
(Elsevier B.V., 2025) Vipin Kumar; Manisha Nidhar; Muhammad Sheraj; Vishal Prasad Sharma; Priya Gupta; Rahul Kumar Singh; Ashish Kumar Tewari
In this study, 1,2,3-triazole-containing six symmetrical flexible dimer compounds (5a-5f) linked via ortho xylyl spacers were synthesized using a copper-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction. Triazinone, isatin, and pyridazinone moieties were utilized to synthesize the heteroaromatic terminal alkynes (3a-3f). The structural characterization of all compounds was performed using spectroscopic techniques, including SCXRD, 1H and 13C-NMR, IR, and HRMS spectrometry. Among these compounds, compound 5a was crystallized, showing two twisted boat-type geometries at an angle of 43.98 degrees. Moreover, we investigated the intra- and intermolecular contact preserving the crystal packing in the solid state. Hirshfeld surface analysis and its related 2-D fingerprint plots control the percentage contribution of intermolecular contact. The in silico study of these compounds was conducted and revealed that 5d and 5c have good docking scores and interactions; further, all these compounds were validated by in vitro DPP-4 inhibitory activity. DPP-4 inhibition revealed that compound 5d has an IC50 value of 1.57 nM, similar to the standard drug sitagliptin. Compound 5d could be a potent DPP-4 inhibitor with antidiabetic potential for further investigation. © 2025
Designing symmetrically folded scaffolds of pyridazinone and triazinone derivatives linked via N,N-diethyl-4-nitro-benzenesulfonamide to explore luminescent materials
(Royal Society of Chemistry, 2025) Vipin Kumar; Krishanu Bandyopadhyay; Manisha Nidhar; Vishal Prasad Sharma; Priyanka Yadav; Suman Gill; Priyanka K. Sonker; Abhineet Verma; Satyen Saha; Ashish Kumar Tewari
The study investigates π⋯π interaction in an aromatic-heteroaromatic folded scaffold as well as (NO)π⋯π(arene) and O⋯π(arene) of pyridazinone and 1,2,4-triazinone and their implication for the design of luminescent materials. The research is focused on elucidating the materials' emission spectra and specifically emphasizing the donor-accepter stacking phenomena in the synthesized compounds by altering heteroaromatic units. The studies enlightened the effect of the methoxy group on emission spectra obtained by flipping the DPM molecule in the liquid and solid phases. Results highlight the importance of intramolecular and intermolecular interactions in determining the optical and electrical properties of organic materials. The full spectral profile and quantum yield (φ) of all compounds were examined in the liquid state. Crystallographic data for compounds DP, DT, DPM, and DTM are presented, highlighting the distinct conformers and stacking strength and affirming the stability of crystal geometry. Furthermore, theoretical studies established the correlation between molecular structure and the absorption spectra of molecules. © 2025 The Royal Society of Chemistry.
Diabetes Mellitus
(Elsevier, 2025) Manisha Nidhar; Ashish Kumar Tewari
Diabetes Mellitus: Target Enzymes and Drugs highlights the importance of different targets in lead drug discovery and the importance of the synthesis of lead analogues. The book discusses the role of target enzymes, receptors, and related drugs in diabetes mellitus that are necessary for research on improving solutions for diabetes care. This unique resource provides information about all enzymes or receptors involved in diabetes pathophysiology to help describe target enzymes and potent antidiabetic drugs to improve patient care. This type of research is needed for the understanding of the effects of drugs in order to improve future treatments and care of patients with diabetes. © 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
Docking Simulation and Anti-Inflammatory Profile of Some Synthesized Heterodimer of Pyrazole
(Pleiades journals, 2020) Pratima Yadav; Ranjeet Kumar; Ashish Kumar Tewari
Abstract: In the present studies, novel pyrazole derivatives have been synthesized linked through various linkers for the anti-inflammatory evaluation. The anti-inflammatory evaluation have been carried out by molecular docking and in vivo experimental models. The docking studies of these synthesized compounds have been performed with the active site of COX-2 compared to celecoxib and in vivo on carrageenan induced rat paw edema. Among all compounds (VIa and VIb) shown good anti-inflammatory activity. © 2020, Pleiades Publishing, Ltd.
Dual role of drugs: beneficial and harmful aspects
(Elsevier, 2018) Sunil Kumar Rai; Ashish Kumar Tewari
Drugs are the compounds used for treatment of diseases; but when found having side-effects such as addiction, there starts their harmful effects on the body, the phenomenon of what is called drug abuse. This chapter is confined to those drugs that were isolated from natural resources or being derived from them, and have their medical applications as well as abuse. We have described from their historical background the chemical and biosyntheses. Herein, we have reviewed amphetamine, charas, cocaine, heroin, and lysergic acid diethylamide in detail. © 2018 Elsevier Ltd. All rights reserved.
Emerging trends in molecular recognition: Utility of weak aromatic interactions
(2008) Ashish Kumar Tewari; Rashmi Dubey
Aromatic interactions play a vital role in chemistry and biology. As about 20% are aromatic in nature, so the role of aromatic interactions become prominent in drug receptor interactions. Not only in drug receptor interactions but also in crystal engineering, protein folding, stacking interactions in DNA/RNA the role of the interactions is of utmost importance. With the emergence of supramolecular chemistry dendrimers, tweezers, rotaxanes, catenanes, and several supramolecular aggregates are associated with aromatic interactions. The mechanism of such interactions is still unknown by the replacement of a small substituent from the aromatic molecule may lead or destroy the interactions. In the present review several models are being discussed with arene interactions under selected heads. © 2007 Elsevier Ltd. All rights reserved.
Erratum: 2-Substituted-8-methyl-3,6-dihydroimidazo [4,5-c]pyrazolo[3,4-e]pyridazine as an anti-inflammatory agent (Medical Chemistry Research DOI: 10.1007/s00044-010-9452-9)
(Birkhauser Boston, 2011) Ashish Kumar Tewari; Rashmi Dubey; Anil Mishra
[No abstract available]