The recent progress of isoxazole in medicinal chemistry

Zhu, Jie; Mo, Jun; Lin, Hongzhi; Yao, Chen; Sun, Haopeng

doi:10.1016/j.bmc.2018.05.013

Cited by 294 publications

(142 citation statements)

References 76 publications

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“…For example, NVP-AUY922 ( Figure 1A) is an anticancer agent [1] and thiophen-2-yl isoxazole ( Figure 1B) significantly inhibits proliferation of HeLa cells. Isoxazole with a steroid moiety ( Figure 1C) has displayed considerable cytotoxicity towards tumor cell lines and sulfisoxazole, flucloxacillin, dicloxacillin, oxacillin, sulfamethoxazole and cloxacillin are some examples of marketed antimicrobial drugs bearing an isoxazole ring [8]. Valdecoxib ( Figure 1D) is a nonsteroidal anti-inflammatory drug (NSAID) that was targeted towards cyclooxygenase enzymes to hinder prostaglandin biosynthesis and to reduce pain [8].…”

Section: Introductionmentioning

confidence: 99%

“…Isoxazole with a steroid moiety ( Figure 1C) has displayed considerable cytotoxicity towards tumor cell lines and sulfisoxazole, flucloxacillin, dicloxacillin, oxacillin, sulfamethoxazole and cloxacillin are some examples of marketed antimicrobial drugs bearing an isoxazole ring [8]. Valdecoxib ( Figure 1D) is a nonsteroidal anti-inflammatory drug (NSAID) that was targeted towards cyclooxygenase enzymes to hinder prostaglandin biosynthesis and to reduce pain [8]. About thirty patents covering different isoxazole-based structures have been reported showing a wide array of chemical modifications and applications of such compounds [8][9][10][11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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Telodendrimer-Based Macromolecular Drug Design using 1,3-Dipolar Cycloaddition for Applications in Biology

et al. 2020

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An architectural polymer containing hydrophobic isoxazole-based dendron and hydrophilic polyethylene glycol linear tail is prepared by a combination of the robust ZnCl2 catalyzed alkyne-nitrile oxide 1,3-dipolar cycloaddition and esterification chemistry. This water soluble amphiphilic telodendrimer acts as a macromolecular biologically active agent and shows concentration dependent reduction of glioblastoma (U251) cell survival.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Telodendrimer-Based Macromolecular Drug Design using 1,3-Dipolar Cycloaddition for Applications in Biology

et al. 2020

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“…Isoxazoles are considered privileged scaffolds in drug discovery and have a broad spectrum of activities—including antibacterial, antiviral, anti‐inflammatory, antimycobacterial—and more recently, they have also demonstrated antitrypanosomal activity…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, antileishmanial, and antifungal biological evaluation of novel 3,5‐disubstituted isoxazole compounds based on 5‐nitrofuran scaffolds

Trefzger

Barbosa

Scapolatempo

et al. 2019

Archiv der Pharmazie

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Nineteen 3,5-disubstituted-isoxazole analogs were synthesized based on nitrofuran scaffolds, by a [3 + 2] cycloaddition reaction between terminal acetylenes and 5-nitrofuran chloro-oxime. The compounds were obtained in moderate to very good yields (45-91%). The antileishmanial activity was assayed against the promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. Alkylchlorinated compounds 14p-r were active on both the promastigote and amastigote forms, with emphasis on compound 14p, which showed strong activity against the amastigote form (IC 50 = 0.6 μM and selectivity index [SI] = 5.2). In the alkyl series, compound 14o stands out with an IC 50 = 8.5 μM and SI = 8.0 on the amastigote form. In the aromatic series, the most active compounds were those containing electron-donor groups, such as trimethoxy isoxazole 14g (IC 50 = 1.2 μM and SI = 20.2); compound 14h, with IC 50 = 7.0 μM and SI = 6.1; and compound 14j containing the 4-SCH 3 group, with IC 50 = 5.7 μM and SI = 10.2. In addition, the antifungal activity of 19 nitrofuran isoxazoles was evaluated against five strains of Candida (C. albicans, C. parapsilosis, C. krusei, C. tropicalis, and C. glabrata). Eleven isoxazole derivatives were active against C. parapsilosis, and compound 14o was found to be the most active (minimal inhibitory concentration [MIC] = 3.4 μM) for this strain. Compound 14p was active against all the strains tested, with an MIC = 17.5 μM for C. glabrata, lower than that of the fluconazole used as the reference drug. K E Y W O R D S5-nitrofuran scaffolds, antifungal activity, antileishmanial activity, drug design, isoxazole core *Ozildéia S. Trefzger, Natália V. Barbosa, and Renata L. Scapolatempo contributed equally to this work.

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“…The scope of heterocycles has been more recently widened with the development of the 1,3‐dipolar cycloaddition between an alkyne and a nitrile oxide, leading to a 1,2 isoxazole ring. The latter enabled therapeutic applications, such as analgesic, anti‐inflammatory,, Anti‐depressant,, and antibacterial, uses, among many others . Moreover, peptides are generally highly flexible; this feature decreases their ability to adopt a specific bioactive conformation and hampers their biological activity.…”

Section: Introductionmentioning

confidence: 99%

Regioselective Solid‐Phase Synthesis of Peptide Analogues Containing 3,4‐ or 3,5‐Disubstituted Isoxazole as s‐cis or s‐trans Peptide Bond Mimics

2019

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A method for regioselective solid‐phase synthesis of disubstituted peptidoisoxazoles is reported. Improved conditions for the synthesis of 3,5‐disubstituted isoxazoles (mimicking s‐trans peptide bond) without metal catalysts were implemented. New conditions enabling the synthesis of 3,4‐disubstituted isoxazoles (mimicking s‐cis peptide bond) using ruthenium catalysts were developed. This study provides a means for the regioselective preparation of new libraries of peptidomimetic molecules containing an isoxazole moiety within the backbone.

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The recent progress of isoxazole in medicinal chemistry

Cited by 294 publications

References 76 publications

Telodendrimer-Based Macromolecular Drug Design using 1,3-Dipolar Cycloaddition for Applications in Biology

Telodendrimer-Based Macromolecular Drug Design using 1,3-Dipolar Cycloaddition for Applications in Biology

Design, synthesis, antileishmanial, and antifungal biological evaluation of novel 3,5‐disubstituted isoxazole compounds based on 5‐nitrofuran scaffolds

Regioselective Solid‐Phase Synthesis of Peptide Analogues Containing 3,4‐ or 3,5‐Disubstituted Isoxazole as s‐cis or s‐trans Peptide Bond Mimics

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