“Azole” as privileged heterocycle for targeting the inducible <i>cyclooxygenase</i> enzyme

Prasher, Parteek; Sharma, Mousmee

doi:10.1002/ddr.21753

Cited by 11 publications

(7 citation statements)

References 147 publications

(158 reference statements)

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“…Azoles have excellent physicochemical benefits for creating biologically active compounds and might generate a variety of noncovalent interactions with biological targets. [ 43,44 ] Mechanistically, azoles can suppress tumor proliferation, invasion, and metastasis by regulating many signaling pathways, making them attractive scaffolds for the establishment of innovative anti‐BC targets. [ 45,46 ] Therefore, indole/isatin‐azole hybrids with a sensible design could result in beneficial therapeutic approaches targeting BC.…”

Section: Indole/isatin‐azole Hybridsmentioning

confidence: 99%

The anti‐breast cancer potential of indole/isatin hybrids

Wang,

Huang,

Yuan

et al. 2023

Archiv der Pharmazie

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Breast cancer (BC) is one of the most prevalent malignancies and the major contributor to cancer mortality in women globally, with a high degree of heterogeneity and a dismal prognosis. As drug resistance is responsible for most BC fatalities and advanced BC is currently considered incurable, finding innovative anti‐BC chemotherapeutics is urgently required. Indole and its analog isatin (indole‐1H‐2,3‐dione) are prominent pharmacophores in the development of novel medications, and their derivatives exhibit strong anticancer activities, also against BC. In particular, indole/isatin hybrids exhibit significant potency against BC including multidrug‐resistant forms and excellent selectivity by influencing a variety of biological targets associated with the disease, supplying helpful building blocks for the identification of potential new BC treatment options. This review includes articles from 2020 to the present and provides insights into the in vitro and in vivo anti‐BC potential, molecular mechanisms, and structure–activity relationships (SARs) of indole/isatin hybrids that may be helpful in the development of innovative anti‐BC chemotherapeutics.

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Section: Indole/isatin‐azole Hybridsmentioning

confidence: 99%

The anti‐breast cancer potential of indole/isatin hybrids

Wang,

Huang,

Yuan

et al. 2023

Archiv der Pharmazie

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“…Encouraged by the aforementioned organocatalyzed intramolecular cycloaddition reactions of VQM intermediates, we then started the atroposelective construction of other axially chiral heterocycles through the formation of five-membered rings. We chose 1,2-azoles as target molecules because they were found in pharmaceuticals approved by FDA, functional materials, and so on …”

Section: Applications Of Vinylidene Ortho-quinone Methides In Enantio...mentioning

confidence: 99%

Enantioselective Synthesis of Atropisomers via Vinylidene ortho-Quinone Methides (VQMs)

2022

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Conspectus Atropisomers, arising from conformational restriction, are inherently chiral due to the intersecting dissymmetric planes. Since there are numerous applications of enantiopure atropisomers in catalyst design, drug discovery, and material science, the asymmetric preparation of these highly prized molecules has become a flourishing field in synthetic chemistry. A number of catalysts, synthetic procedures, and novel concepts have been developed for the manufacture of the atropisomeric molecules. However, due to the intrinsic properties of different types of atropisomers featuring biaryl, hetero-biaryl, or non-biaryl architectures, only very few methods pass the rigorous inspection and are considered generally applicable. The development of a broadly applicable synthetic strategy for various atropisomers is a challenge. In this Account, we summarize our recent studies on the enantioselective synthesis of atropisomers using the vinylidene ortho-quinone methides (VQMs) as pluripotent intermediates. The most appealing features of VQMs are the disturbed aromaticity and axial chirality of the allene fragment. At the outset, the applications of VQMs in organic synthesis have been neglected due to their principal liabilities: ephemeral nature, extraordinary reactivity, and multireaction sites. The domestication of this transient intermediate was demonstrated by in situ catalytic asymmetric generation of VQMs, and the reactivity and selectivity were fully explored by judiciously modifying precursors and tuning catalytic systems. A variety of axially chiral heterocycles were achieved through five-, six-, seven- and nine-membered ring formation of VQM intermediates with different kinds of branched nucleophilic functional groups. The axially chiral C–N axis could be constructed from VQM intermediates via N-annulation or desymmetrization of preformed C–N scaffolds. We take advantage of the high electrophilicity of VQMs toward a series of sulfur and carbon based nucleophiles leading to atropisomeric vinyl arenes. Furthermore, chiral helical compounds were realized by cycloaddition or consecutive annulation of VQM intermediates. These achievements demonstrated that the VQMs could work as a nuclear parent for the collective synthesis of distinct and complex optically active atropisomers. Recently, we have realized the isolation and structural characterization of the elusive VQMs, which were questioned as putative intermediates for decades. The successful isolation of VQMs provided direct evidence for their existence and an unprecedented opportunity to directly investigate their reactivity. The good thermal stability and reserved reactivity of the isolated VQMs demonstrated their great potential as synthetic reagents and expanded the border of VQM chemistry.

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“…The introduction of azole fragments has a wide perspective due to their ability to form various noncovalent interactions with different therapeutic targets, which is valuable for drug design. Different azole derivatives have significant potential for medicinal chemistry [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. Of particular interest are 1 H -1,2,4-triazole and imidazole derivatives, which are known to possess therapeutic effect against drug-resistant pathogens [ 40 , 41 , 42 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Mono- and Polyazole Hybrids Based on Polyfluoroflavones

et al. 2023

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The possibility of functionalization of 2-(polyfluorophenyl)-4H-chromen-4-ones, with them having different numbers of fluorine atoms, with 1,2,4-triazole or imidazole under conditions of base-promoted nucleophilic aromatic substitution has been shown. A high selectivity of mono-substitution was found with the use of an azole (1.5 equiv.)/NaOBut(1.5 equiv.)/MeCN system. The structural features of fluorinated mono(azolyl)-substituted flavones in crystals were established using XRD analysis. The ability of penta- and tetrafluoroflavones to form persubstituted products with triazole under azole (6 equiv.)/NaOBut(6 equiv.)/DMF conditions was found in contrast to similar transformations with imidazole. On the basis of mono(azolyl)-containing polyfluoroflavones in reactions with triazole and pyrazole, polynuclear hybrid compounds containing various azole fragments were obtained. For poly(pyrazolyl)-substituted flavones, green emission in the solid state under UV-irradiation was found, and for some derivatives, weak fungistatic activity was found.

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“Azole” as privileged heterocycle for targeting the inducible cyclooxygenase enzyme

Cited by 11 publications

References 147 publications

The anti‐breast cancer potential of indole/isatin hybrids

The anti‐breast cancer potential of indole/isatin hybrids

Enantioselective Synthesis of Atropisomers via Vinylidene ortho-Quinone Methides (VQMs)

Synthesis of Mono- and Polyazole Hybrids Based on Polyfluoroflavones

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