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      The synthetic and therapeutic expedition of isoxazole and its analogs

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          Abstract

          Isoxazole, constituting an important family of five-membered heterocycles with one oxygen atom and one nitrogen atom at adjacent positions is of immense importance because of its wide spectrum of biological activities and therapeutic potential. It is, therefore, of prime importance that the development of new synthetic strategies and designing of new isoxazole derivatives should be based on the most recent knowledge emerging from the latest research. This review is an endeavor to highlight the progress in the chemistry and biological activity of isoxazole derivatives which could provide a low-height flying bird’s eye view of isoxazole derivatives to the medicinal chemists for the development of clinically viable drugs using this information.

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          Most cited references172

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          Isoxazole ring as a useful scaffold in a search for new therapeutic agents

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            Development of Pyrazolone and Isoxazol-5-one Cambinol Analogues as Sirtuin Inhibitors

            Sirtuins are a family of NAD+-dependent protein deacetylases that play critical roles in epigenetic regulation, stress responses, and cellular aging in eukaryotic cells. In an effort to identify small molecule inhibitors of sirtuins for potential use as chemotherapeutics as well as tools to modulate sirtuin activity, we previously identified a nonselective sirtuin inhibitor called cambinol (IC50 ≈ 50 μM for SIRT1 and SIRT2) with in vitro and in vivo antilymphoma activity. In the current study, we used saturation transfer difference (STD) NMR experiments with recombinant SIRT1 and 20 to map parts of the inhibitor that interacted with the protein. Our ongoing efforts to optimize cambinol analogues for potency and selectivity have resulted in the identification of isoform selective analogues: 17 with >7.8-fold selectivity for SIRT1, 24 with >15.4-fold selectivity for SIRT2, and 8 with 6.8- and 5.3-fold selectivity for SIRT3 versus SIRT1 and SIRT2, respectively. In vitro cytotoxicity studies with these compounds as well as EX527, a potent and selective SIRT1 inhibitor, suggest that antilymphoma activity of this compound class may be predominantly due to SIRT2 inhibition.
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              One-pot copper(I)-catalyzed synthesis of 3,5-disubstituted isoxazoles.

              [reaction: see text] 3,5-Disubstituted isoxazoles are obtained in good yields by a convenient one-pot, three-step procedure utilizing a regioselective copper(I)-catalyzed cycloaddition reaction between in situ generated nitrile oxides and terminal acetylenes. Most functional groups do not interfere with the reaction, which can be performed in aqueous solvents without protection from oxygen. Since all reagents are used in stoichiometric amounts, formation of byproducts is minimized.
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                Author and article information

                Contributors
                kumkumagr.1990@gmail.com
                Journal
                Med Chem Res
                Med Chem Res
                Medicinal Chemistry Research
                Springer US (New York )
                1054-2523
                1554-8120
                27 February 2018
                2018
                : 27
                : 5
                : 1309-1344
                Affiliations
                GRID grid.448881.9, Institute of Pharmaceutical Research, , GLA University, ; Mathura, U.P. India
                Article
                2152
                10.1007/s00044-018-2152-6
                7079875
                32214770
                1d586710-2a55-492a-a1ff-aae8c797546e
                © Springer Science+Business Media, LLC, part of Springer Nature 2018

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 22 November 2017
                : 1 February 2018
                Categories
                Review Paper
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2018

                Pharmaceutical chemistry
                heterocyclic,isoxazole,biological activity,anticancer,anti-inflammatory,antimicrobial

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