Design of a Heteroaryl Modified, 1,5-Disubstituted Pyrazole Cyclooxygenase-2 (COX-2) Selective Inhibitor

Ezawa, Masahiko; Garvey, David S.; Janero, David R.; Khanapure, Subhash P.; Letts, L. Gordon; Martino, Allison M.; Ranatunge, Ramani R.; Schwalb, David J.; Young, Delano V.

doi:10.2174/1570180053398451

Cited by 18 publications

(9 citation statements)

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“…Heterocycles containing the pyrazole moiety have exhibited diverse biological activities that include anti-depressant, anti-convulsant, 62 anti-inflammatory and anti-arthritic 63 activities. A simple, efficient, and environmentally benign protocol was developed for the synthesis of 1,3,5-triarylpyrazoles (18) via the one-pot oxidative addition of chalcones (16) came out to be superior in terms of both reaction time as well as product yields.…”

Section: Synthesis Of 135-triarylpyrazolesmentioning

confidence: 99%

[Bmim]PF6: An efficient tool for the synthesis of diverse bioactive heterocycles

Kaur¹,

Sharma²,

Banerjee³

2018

J Serb Chem Soc

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Heterocycles are the privileged structural subunit of many marketed drug molecules. On the other hand, the last decade has seen tremendous applications of the ionic liquid [bmim]PF 6 (1-butyl-3-methyl-1H-imidazolium hexafluorophosphate) as an efficient, cheap, commercially available, low toxic reaction medium for various organic transformations. The present review summarizes recent reported applications of [bmim]PF 6 as an efficient reaction medium for the synthesis of diverse biologically relevant heterocycles.

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Section: Synthesis Of 135-triarylpyrazolesmentioning

confidence: 99%

[Bmim]PF6: An efficient tool for the synthesis of diverse bioactive heterocycles

Kaur¹,

Sharma²,

Banerjee³

2018

J Serb Chem Soc

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“…Pyrazole derivatives have a long history of applications in agriculture as herbicides and insecticides as well as in the pharmaceutical industry as antipyretic and anti-inflammatory agents [7][8][9][10][11][12]. Pyrazole derivatives have been reported to show a broad spectrum of biological activity including antibacterial [13], antifungal [14], analgesic [15], anti-inflammatory [16][17][18], neuroprotective [19], estrogen receptor binding [20], antineoplastic [21], activities. Due to their wide range of biological activities, pyrazoles received considerable interest in the field of drug discovery and therefore pyrazole ring constitutes a relevant synthetic target in the pharmaceutical industry.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Molecular Docking, Admet Studies and Biological Evaluation of Pyrazoline Incorporated 1, 2, 3-Triazole Benzene Sulphonamides

Siliveri

Bashaboina

Vamaraju

et al. 2019

Int J Pharm Pharm Sci

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Objective:The main objective of this work was to design, synthesize and evaluate the novel pyrazoline incorporated 1,2,3-triazole benzene sulphonamides for cytotoxic and anti-gout activities also to perform Insilco molecular docking studies.Methods: Designed compounds were synthesized by condensation of different substituted chalcones (3a-i) with hydrazine hydrate and substituted phenylhydrazines. All the synthesized compounds were characterized on the basis of physical and spectral data. To predict the affinity and activity of the ligand molecule Libdock program was employed to generate different bioactive binding poses of designing molecules at the active site of protein Phosphatidylinositol 3-kinase (PI3Kα). Title compounds were evaluated for cytotoxic activity by using 3-(4, 5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) assay and anti-gout activity by potassium oxonate induced assay.Results: All the synthesized compounds showed characteristic peaks in FTIR, 1 H, 13 C NMR and MASS spectral analysis. In molecular docking studies, compound 3i has shown good binding affinity to the active site of PI3Kα with a docking score of 145.031 and 4 hydrogen bonding interactions with least hepatotoxicity and good bioavailability when compared with that of reference ligand KKR exhibited a Libdock score of 88.35. Remaining compounds also have a good binding affinity with a minimum of 2 bonding interactions and having better absorption, distribution, metabolism, elimination and toxicity (ADMET) profile. The same compound (3i) exhibited the highest cytotoxic activity with an IC50 value of 4.54µg/ml. Compound 4d was evaluated for anti-inflammatory activity and it has significantly ameliorated against potassium oxonate induced gout in mice when compared with that of standard drug allopurinol due to its anti-inflammatory property. Conclusion:We designed and synthesized a novel series of title compounds in quantitative yields and performed docking studies. New derivatives have a good binding affinity towards PI3Kα enzyme, good bioavailability, least hepatotoxicity and significant cytotoxic activity.

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“…Moreover, several pyrazole ring systems are associated with antifungal, antitubercular, antibacterial, antiviral, anticancer, and antioxidant activities . Pyrazolotriazine ring systems were reported to exhibit several biological activities .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antioxidant Evaluation of Some New Pyridopyrazolotriazine Derivatives

Gouda

2014

Journal of Heterocyclic Chem

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Diazodization of pyrazolo[3,4‐b]pyridine 1 afforded diazonium salt 2 that coupled with active methylene compounds such as 3a,3b, 6, 7, 8, 15a,15b, 16a,16b, 17, and 24 in pyridine to give aryl hydrazone derivatives 4a,4b, 9, 10, 11, 18a, 18b, 19a,19b, 20, and 25, respectively. The previous synthesized compounds underwent cyclization in acetic acid to give the corresponding pyridopyrazolotriazines 5a,5b, 12, 13, 14, 21a,21b, 22a, 22b, 22c, 23, and 26, respectively. The newly synthesized compounds were characterized by elemental analysis and spectral data and screened for their antioxidant activities. The results of ABTS method showed clearly that compounds 1, 4b, 5b, 11, 20, 25, and 26 displayed promising in vitro antioxidant activities. Compounds 1 and 4a exhibited high protection against DNA damage induced by the bleomycine iron complex.

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Design of a Heteroaryl Modified, 1,5-Disubstituted Pyrazole Cyclooxygenase-2 (COX-2) Selective Inhibitor

Cited by 18 publications

References 0 publications

[Bmim]PF6: An efficient tool for the synthesis of diverse bioactive heterocycles

[Bmim]PF6: An efficient tool for the synthesis of diverse bioactive heterocycles

Design, Synthesis, Molecular Docking, Admet Studies and Biological Evaluation of Pyrazoline Incorporated 1, 2, 3-Triazole Benzene Sulphonamides

Synthesis and Antioxidant Evaluation of Some New Pyridopyrazolotriazine Derivatives

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