The discovery of oxazolones-grafted spirooxindoles via three-component diversity oriented synthesis and their preliminary biological evaluation

Dong, Hui; Song, Sicheng; Li, Jingjing; Xu, Chao; Zhang, Haowei; Ouyang, Liang

doi:10.1016/j.bmcl.2015.06.076

Cited by 36 publications

(11 citation statements)

References 30 publications

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“…The 3,3’-spiropyrrolidinyloxindole unit is found in the molecular skeleton of a large family of natural alkaloids with remarkable bioactivity profiles and interesting structural properties [19–20]. Derivatives with the 2,3’-spiropyrrolidinyloxindole core show various biological effects such as bactericidal and fungicidal [21], anticancer [22], cytotoxic to MCF-7 and HepG2 cells [23–24], and advanced glycation end (AGE) product formation inhibitory activities [25] (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

“…Over the last decade, a lot of publications have been devoted to the synthesis of dispiro compounds comprising pyrrolidine, oxindole, and other heterocycle moieties and to the evaluation of their physiological properties [24,26–32]. In this regard, our attention was directed towards hetero-annelated 1,2,4-triazines, because this motif is part of many natural and synthetic bioactive products [33–40].…”

Section: Introductionmentioning

confidence: 99%

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An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

Izmest’ev

Газиева

Sigay

et al. 2016

Beilstein J. Org. Chem.

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An effective and highly regio- and diastereoselective one-pot method for the synthesis of new polynuclear dispiroheterocyclic systems with five stereogenic centers (dispiro[imidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine-6,3′-pyrrolidine-2′,3′′-indoles]) comprising pyrrolidinyloxindole and imidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine moieties has been developed. The method relies on a 1,3-dipolar cycloaddition of azomethine ylides generated in situ from isatin derivatives and sarcosine to 6-benzylideneimidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine-2,7-diones.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

Izmest’ev

Газиева

Sigay

et al. 2016

Beilstein J. Org. Chem.

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“…N ‐ and O ‐Heterocycles are of prime interest as useful ligands to biological systems and as drug candidates in biological and pharmaceutical research. 2‐Oxazolones represent one of the most desirable structural motifs for such compounds, and they also serve as important building blocks and intermediates for complex molecule construction, including natural products– and their analogues. We now investigated the reactivity of the olefinic bond of 2‐oxazolones ( I ) and discovered a one‐step BF 3 ⋅Et 2 O/H 2 O‐catalyzed synthesis of N , O ‐heterocycles of type II and diastereoselective construction of tetracyclic compounds of type III (Scheme )…”

Section: Methodsmentioning

confidence: 99%

Efficient Synthesis of Dimeric Oxazoles, Piperidines and Tetrahydroisoquinolines from N‐Substituted 2‐Oxazolones

Agarwal

Kiran

et al. 2016

Chemistry A European J

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A mild and practical method for the construction of heterocycles from N-substituted 2-oxazolones through cascade, BF3 ⋅Et2 O/H2 O-catalyzed reactions involving iminium ion generation and trapping by external or internal olefinic and aryl moieties is described. Mechanistic and computational studies revealed the strong protic acid HBF4 as the initiating catalyst for these cascade reactions. Providing access to novel molecular diversity, these processes may facilitate chemical biology studies, drug discovery efforts and natural products synthesis.

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“…The spirocyclic core structures have been recognized as promising scaffolds in drug discovery due to reduced conformational entropy and capacity to bind to a protein targets . In this regard, spirooxindoles have been considered as drug leads by many researchers as many pharmaceutically validated natural alkaloids, and other biologically relevant compounds posses this moiety . The oxindole motif structure has the reactive site at the C3 which can be easily be used to construct fused heterocyclic motifs.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Oxindole Analogues, Biological Activity, and In Silico Studies

et al. 2019

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Highly divergent complexity molecules, having spirooxindole core structure, possess excellent bioactivities. The 1,3-dipolar cycloaddition reaction is one of the most efficient approach for the rapid synthesis of spirooxindole analogues. Herein, we report the synthesis of a series of spirooxindolone analogues via multicomponent reaction of chalcone, based on cyclohexanone, substituted isatin (isatin, 5-Cl-isatin, and 5-Br-isatin), and secondary amine of the amino acids (L-Proline and Thioproline). The included activities of the resulting spirooxazolines, including anti-inflammatory, anti-leishmanial, and cytotoxic activity against 3T3 and HeLa cell lines. Among series of nine diphenyl substituted derivatives of spiro fused benzylidine thioazol indolines (IVa-IVi), compounds IVb (IC 50 = 5.8 � 0.9 μM), IVc (IC 50 = 2.4 � 1.3 μM), IVd (IC 50 = 5.0 � 0.6 μM), and IVg (IC 50 = 10.4 � 4.6 μM) have shown potent anti-inflammatory activity, several fold more active than the standard drug, ibuprofen (IC 50 = 11.2 � 1.9 μM). Whereas, compounds IVa (IC 50 = 18.0 � 1.1 μM), and IVh (IC 50 = 26.0 � 3.4 μM) exhibited a significant anti-inflammatory potential. All other compounds (IVe and IVf) were found to be inactive. Two meta flouro substituted phenyl rings containing compound IVc (IC 50 = 2.4 � 1.3 μM) was the most potent member of the series. In order to rationalize the observed biological activities of the spirooxindole-pyrrolothiazole derivatives, in silico studies were also performed. The results of present study identify a new series of potent anti-inflammatory agents, deserve to be further investigated as leads.[a] G. Lotfy, Dr. Y. M. A. Aziz, Prof. M. M. Said have shown a significant anti-inflammatory potential. All other compounds (VId and VIe) were found to be inactive. Two ortho, meta dichloro substituted phenyl rings containing compound VIc (IC 50 = 4.2 � 1.8 μM) was found to be the most active Scheme 1. Synthesis of target thioazol/pyrrol indolines analogues IVa-i and VIa-h.

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The discovery of oxazolones-grafted spirooxindoles via three-component diversity oriented synthesis and their preliminary biological evaluation

Cited by 36 publications

References 30 publications

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

Efficient Synthesis of Dimeric Oxazoles, Piperidines and Tetrahydroisoquinolines from N‐Substituted 2‐Oxazolones

Synthesis of Oxindole Analogues, Biological Activity, and In Silico Studies

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