Synthesis and pharmacological evaluation of aminoacetylenic isoindoline-1,3-dione derivatives as anti-inflammatory agents (original) (raw)
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Analgesic and Toxicity Studies of Aminoacetylenic Isoindoline-1, 3-dione Derivatives
ISRN pharmacology, 2012
We have developed a series of aminoacetylenic isoindoline-1, 3-dione compounds and showed their anti-inflammatory activities by reducing carrageenan-induced rat paw edema and modulating proinflammatory and anti-inflammatory cytokines. In the present study and due to efficacy reasons, we are exploring only two of these compounds, namely, ZM4 and ZM5, to reveal their analgesic activity and toxicity. Following oral administration, both compounds were effective in reducing significantly (–0.001) acetic acid-induced writhing ...
International Immunopharmacology, 2012
We recently designed series of N-[4-(t-amino-yl)-but-2-yn-1-yl] isoindoline-1, 3-diones as anti-inflammatory compounds, called ZM compounds. These ZM compounds were categorized according to the nature of the cyclic amino groups into ZM2, ZM3, ZM4, and ZM5 and were shown to reduce carrageenan-induced inflammation, inhibit cyclooxygenase (1 and 2) and have less adverse effects than the common non-steroidal anti-inflammatory drugs. In the present study, we are examining the potential effects of ZM compounds in ...
Arkivoc, 2013
Searching new targets for anti-inflammatory drug design, agents with the isoindole skeleton were focused on the basis of preliminary studies of NSAIDs as COX-1 and/or COX-2 enzyme inhibitors. Thus several novel N-substituted isoindoline derivatives as possible biologically active compounds were prepared as analogues of Indoprofen (1) starting from cis-2-[(4methylphenyl)carbonyl]cyclohexanecarboxylic acid (3) by treatment with primary arylamines.
Archiv der Pharmazie, 2011
In an effort to establish new candidates with improved analgesic and anti-inflammatory activities, we reported here the synthesis and in-vivo analgesic and anti-inflammatory evaluation of various series of 2-substituted-3a,4,9,9a-tetrahydro-4,9-benzeno-benz[f]isoindole-1,3-diones: [4-Bromobutoxy] 6, 5-bromopentoxy 7, [4-(4-phenylpiperazin-1-yl)butoxy] 9, [5-(4-phenylpiperazin-1-yl)pentoxy] 10, 2-(2(4)-(4-phenylpiperazin-1-yl)-2-oxoethyl/4-oxobutyl 17, 19, [2(4)-(4-methylpiperazin-1-yl]-2-oxoethyl/ 4-oxobutyl 20, 22, [2(4)-morpholino-2-oxoethyl/4-oxobutyl] 23, 25, and 2(4)-(piperidin-1-yl)2-oxoethyl/ 4-oxobutyl) 26 and 28. The newly synthesized compounds were characterized by (IR, 1 H-, 13 C-NMR, and mass spectra). The representative compounds were evaluated as analgesic and anti-inflammatory activities. Compounds 9, 19, 22, 25, and 28 exhibited activities higher than the reference drug.
Processes
Novel phthalimide derivatives, namely N-(1,3-dioxoisoindolin-2-yl)-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide (1a) and N-(1,3-dioxoisoindolin-2-yl)thiophene-2-carboxamide (1b), and hexahydrophthalimide derivative N-(1,3-dioxohexahydro-1H-isoindol-2(3H)-yl)-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide (2), have been synthesized. The phthalimide derivatives were synthesized from phthalic anhydride and 2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetohydrazide or thiophene-2-carbohydrazide, and the hexahydrophthalimide derivative has been synthesized from hexahydrophthalic anhydride and 2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetohydrazide. The chemical structures of the compounds are elucidated by Nuclear Magnetic Resonance (NMR) and Infrared (IR) spectra. The new in vitro antioxidant activities of the obtained substances were evaluated using the DPPH method. All tested compounds showed antioxidative activity, the most active compound being 1b. Bioinformatics tools were used for the pred...
2014
2-(2-Bromoacetyl)isoindoline-1,3-dione 2 and 2-(2-cyanoacetyl)isoindoline-1,3-dione 3 have been used as starting intermediates for synthesis of functionalized heterocyclic derivatives such as, 2-(2-aminothiazol-5-yl)isoindoline-1,3-dione 4, 2-(2-(benzylideneamino)thiazol-5-yl)isoindoline-1,3-dione 5, 2-(2-(3-chloro-2-oxo-4-phenylazetidin-1-yl)thiazol-5yl)isoindoline-1,3-dione 6, 2-(2-(4-oxo-2-phenylthiazolidin-3-yl)thiazol-5-yl)isoindoline-1,3-dione 7, 2-(2-arylhydrazono)2-bromo(cyano)acetyl)-isoindoline-1,3-dione 8, 6-bromo-5-(1,3-dioxoisoindolin-2-yl)-3-oxo-2-phenyl-2,3-dihydropyridazine4-carbonitrile 10a, 4-(1,3-dioxoisoindolin-2-yl)-6-oxo-1-phenyl-1,6-dihydropyridazine-3,5-dicarbonitrile 10b, 1-acetyl-3(1,3-dioxoisoindolin-2-yl)-5-aryl-4,5-dihydro-1H-pyrazole-4-carbonitrile 12, 4-cyano-3-(1,3-dioxoisoindolin-2-yl)-5-aryl4,5-dihydro-1H-pyrazole-1-carbothioamide 13, 3-(1,3-dioxoisoindolin-2-yl)-1-(4-oxo-4,5-dihydrothiazol-2-yl)-5-phenyl4,5-dihydro-1H-pyrazole-4-carbonitrile 14, 3-...
RASAYAN Journal of Chemistry
New decahydroacridine-1,8-dione derivatives have been synthesized from 3-aminocyclohex-2-en-1-one. The compounds were characterized based on spectroscopic data and assessed their antioxidant and anti-inflammatory properties both in-vitro and in-silico. All the compounds exhibited poor in-vitro antioxidant activity but high in-vitro anti-inflammatory activity. An in-silico study using Autodock v 4.2 integrated LigandScout software 4.4.3. against the COX-1 (PBD ID: 1CQE) and COX-2 (PBD ID: 6COX) enzymes indicated that all the compounds could interact with both enzymes. Except for 3c against COX-1, the compounds’ interaction with both enzymes exhibited binding energy lower than diclofenac and curcumin. The results confirm that the compounds have a high potential to be antiinflammatory agents and deserve further development.