Regioselective synthesis and anti-inflammatory activity of novel dispiro[pyrazolidine-4,3'-pyrrolidine-2',3"-indoline]-2",3,5-triones

Abstract

Novel dispiro[pyrazolidine-4,3'-pyrrolidine-2',3"-indoline]-2",3,5-triones 5a-j were obtained regioselectively by 1,3-dipolar cycloaddition reaction of 4-arylidene-1-phenylpyrazolidine-3,5-diones 2a-e as dipolarophiles with non-stabilized azomethine ylides, generated in situ via decarboxylative condensation of isatins 3a,b and sarcosine 4 in dry ethanol. The prepared compounds were screened for their anti-inflammatory activity "at a dose of 10 mg/kg body weight", especially 5d, 5f, 5h, and 5j which reveal remarkable activities relative to indomethacin which was used as a reference standard in this study.

1,3-Dipolar cycloaddition approach to novel dispiro[pyrazolidine-4,3′-pyrrolizidine-2′,3″-indoline]-2″,3,5-triones

“…1-Phenylpyrazolidine-3,5-dione 1 was prepared according to the cyclocondensation reaction of malonic acid and phenylhydrazine in the presence of phosphorus oxychloride; the different substituted (Z)-4-arylidene-1-phenylpyrazolidine-3,5dione derivatives 2a-e 27 were prepared in accordance with the previously reported procedure (Scheme 1). 5,28…”

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Dipolar cycloadditions are an important group of reactions in organic synthesis for building five-membered heterocycles especially substituted pyrrolidine, pyrrolizine, and pyrrolothiazole derivatives. [1][2][3][4][5] The cycloadditions of azomethine ylides which represent one of the most reactive and versatile classes of 1,3-dipoles are trapped readily by a range of dipolarophiles, either intra-or intermolecularly. The use of exocyclic olefins enables the construction of functionalised five-membered spiro heterocycles.

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“…The use of exocyclic olefins enables the construction of functionalised five-membered spiro heterocycles. [5][6][7][8][9][10][11] N-Arylpyrazoles are a very exciting class of heterocyclic compounds that have potent pharmacological activities in many medical fields such as hypoglycemic, 12 antibacterial, antifungal, 13 antitumor, 14 anti-thromboembolic disorders, antiangiogenic 15 and anti-inflammatory effects. 16,17 Pyrrolidine, pyrrolizine, and pyrrolothiazole derivatives are important bioactive heterocyclic compounds which have antimicrobial, antiviral, anti-inflammatory, antitubercular, anticancer, and antidiabetic activities.…”

Ultrasound-assisted, ZnBr2-catalyzed regio- and stereoselective synthesis of novel 3,3′-dispiropyrrolidine bisoxindole derivatives via 1,3-dipolar cycloaddition reaction of an azomethine ylide

“…[1][2][3] In recent years the azomethine ylide has gained a vital place in the synthesis of heterocyclic compounds as it serves as an important building block for the construction of nitrogen-containing five membered heterocycles, [4][5][6][7][8] which are often an integral part of many natural products and bioactive molecules. 9,10 The 3,3′-spirocyclooxindole skeleton is found in a growing number of natural or synthetic products presenting various biological activities. [11][12][13] In particular, the spiropyrrolidinyloxindole, due to its presence in a large number of bioactive alkaloids, such as coerulescine 14,15 (1), inhibitor of the MDM2-p53 16,17 (2), alstonisine 18,19 (3) and strychnofoline 20 (4) display a broad range of biological activity (Figure 1).…”

Investigation and Synthesis of Some Novel Spiro Heterocycles Related to Indoline Moiety

“…From this point of view and in continuation of our previous work [44][45][46][47], our aim is to design some new spiro heterocycles containing indoline moiety with expected high biological activity. Further in this paper we present the full experimental details of some novel spiroheterocycles [48][49][50][51][52][53][54].…”