- Indolyl-isoxazolidines attenuate LPS-stimulated pro-inflammatory cytokines and increase survival in a mouse model of sepsis: Identification of potent lead
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A library of indolyl-isoxazolidines (6–9) has been synthesized by regio- and stereoselective microwave irradiated 1,3-dipolar cycloadditions of C-(3-indolyl)-N-phenylnitrone (2′) with variedly substituted dipolarophiles (3′-5′) and screened for their anti-inflammatory activities through inhibition of pro-inflammatory cytokines such as TNF-α and IL-6. Amongst the evaluated compounds (6–9), bicyclic isoxazolidine (9a) was found to exhibit significant inhibitory potential against LPS induced human IL-6 and TNF-α in THP-1 cells. Compound 9a was further assessed for in vivo analgesic and anti-inflammatory activities via acetic acid induced writhing and carrageenan induced paw edema models in mice, respectively. The results showed that compound possesses potent anti-inflammatory-analgesic activity comparable to indomethacin and did not show toxicity up to a 2000 mg kg?1 dose as evidenced by histopathological studies. Consequently, the most active compound 9a was also evaluated against LPS-induced septic death and exhibited a significant protection in in vivo mouse model. Taken all together, the results suggest that the compound 9a is able to attenuate pro-inflammatory cytokines such as IL-6 and TNF-α; accelerate resolution of inflammation, and also increased survival rate of septic mice. Therefore, these “lead” isoxazolidines can be used as promising candidate for further analgesic/anti-inflammatory drug design and development.
- Singh, Gagandeep,Singh, Gurjit,Bhatti, Rajbir,Gupta, Mehak,Kumar, Ajay,Sharma, Ankita,Singh Ishar, Mohan Paul
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- Investigations on synthesis of indole based constrained mimetic scaffolds through 1,3-dipolar cycloadditions of the C-(3-indolyl)-N-phenylnitrone with a variety of olefinic and allenic dipolarophiles under microwave irradiation
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Monomode microwave assisted regio- and stereo-selective 1,3-dipolar cycloadditions of C-(3-indolyl)-N-phenylnitrone (19) with a number of olefinic dipolarophiles (20a-f) afford isoxazolidines (21-26) in high yields, which are conformationally constrained
- Bhella, Surinderjit Singh,Pannu, Ajay Pal Singh,Elango, Munusamy,Kapoor, Ashish,Hundal, Maninder Singh,Ishar, Mohan Paul S.
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- Formation and reductive ring opening reactions of indolyl bicyclic-isoxazolidines-II:7access to novel natural product analogs
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Attempted reductive cleavage of indolyl-bicyclic-isoxazolidines (4a,b; R?=?benzyl, phenyl) with ammonium formate, methanol-THF solvents, at ambient temperature, in the presence of Pd/C lead to facile synthesis of indolyl-α-hydroxy-γ-lactams (5a–b), derive
- Singh, Gagandeep,Raj, Tilak,Gupta, Vivek,Ishar, Mohan Paul Singh
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- Copper-Catalyzed Synthesis of Polysubstituted Pyrroles through [3+1+1] Cycloaddition Reaction of Nitrones and Isocyanides
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An efficient, copper-catalyzed [3+1+1] cycloaddition reaction was developed for the expedient synthesis of pharmacologically interesting polysubstituted pyrroles from easily available nitrones and α-acidic isocyanides. The given approach features a new mo
- Tian, Zhuang,Xu, Jiaojiao,Liu, Bingxin,Tan, Qitao,Xu, Bin
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supporting information
p. 2603 - 2606
(2018/05/22)
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- Formation and reductive ring opening reactions of indolyl-isoxazolidines: Access to novel natural product analogs and precursors
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Regio- and stereoselective 1,3-dipolar cycloadditions of C-(3-indolyl)-N-phenylnitrone (2) with variedly substituted dipolarophiles were carried out to obtain syn- C4 and C5 substituted indolyl-isoxazolidines 6a-c and 7a-f, respectively. Reduction of obtained isoxazolidines, by employing various reducing agents, causes cleavage of the N-O bond, which is accompanied by concomitant cleavage of C-N bond leading to the formation of a library of novel indole based natural product analogs and precursors.
- Singh, Gagandeep,Sharma, Suresh,Gupta, Vivek,Raj, Tilak,Singh, Palwinder,Ishar, Mohan Paul S.
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p. 900 - 911
(2016/01/28)
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- An unexpected catalytic synthesis of novel and known bis(pyrazolyl) methanes by the use of α-aryl-N-phenyl nitrones in aqueous media
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Reaction of -aryl-N-phenyl nitrones with 3.methyl-1-phenyl-2-pyrazoline-5-one in the presence of a catalytic amount of silica tungstic acid in EtOH/H2O afforded, unexpectedly, high yields of bis(3-hydroxy-1-phenylpyrazolyl)-arylmethanes instead of the two possible 1,3-addition products. This is the first report of the synthesis of bis(3-hydroxy-1-phenylpyrazolyl)-arylmethanes via the reaction of nitrones and a pyrazolin-5-one. A possible mechanism for the process is suggested.
- Eskandari, Khalil,Karami, Bahador,Khodabakhshi, Saeed
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p. 600 - 603
(2014/12/12)
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- Reaction of Aldonitrones with Copper Acetylide : Synthesis of Some Novel β-Lactams
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Nitrones (7a-e) react with copper acetylide (6) to afford cis- and trans-β-lactams (8 and 9) in good yields.The cis- and trans-isomers have been isolated, respectively as the major and minor products and are characterized through spectral data (IR, mass a
- Dutta, D. K.,Boruah, R. C.,Sandhu, J. S.
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p. 350 - 353
(2007/10/02)
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- REACTION OF α-3-INDOLYL NITRONES WITH MALONIC ESTERS, INCLUDING MIGRATION OF THE INDOLE RESIDUE
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The reaction of α-(3-indolyl) N-aryl(alkyl) nitrones with malonic and methylmalonic esters leads to the formation of derivatives of 3-aminoindole, i.e., the esters of β-N-(3-indolyl)-N-aryl(alkyl)aminopropenoic acids.The reaction was extended to 3-indolyl nitrones differing in the substituents at the nitrogen atom and at position 2 of the indole ring.
- Velezheva, V. S.,Yaroslavskii, I. S.,Kurkovskaya, L. N.,Suvorov, N. N.
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p. 1367 - 1376
(2007/10/02)
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