mannich-bases and Edema

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 2; Drug Design; Edema; Humans; Male; Mannich Bases; Mice, Inbred BALB C; Molecular Docking Simulation; Naproxen; Pain; Triazoles

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Edema; Lipopolysaccharides; Mannich Bases; Mice; Nitric Oxide; Rats; RAW 264.7 Cells; Stomach Ulcer

In continuation of structure activity relationship studies, a panel of fluorine containing sydnones with styryl ketone group 4-[1-oxo-3-(substituted aryl)-2-propenyl]-3-(3-chloro-4-fluorophenyl)sydnones 2a-i, was synthesized as better analgesic and anti-inflammatory agents. The title compounds were formed by condensing 4-acetyl-3-(3-chloro-4-fluorophenyl)sydnone with various substituted aryl aldehydes, characterized by spectral studies and evaluated at 100 mg\\kg b.w., p.o. for analgesic, anti-inflammatory and ulcerogenic activities. Compounds 2c and 2e showed good analgesic effect in acetic acid-induced writhing while none showed significant activity in hot plate assay in mice. In carrageenan-induced rat paw oedema test, compound 2c and 2f exhibited good anti-inflammatory effect at 3rd h, whereas compounds 2c, 2e, 2d, 2g and 2h showed activity in croton oil induced ear oedema assay in mice. Compounds 2c and 2e were less ulcerogenic than ibuprofen in rats, when tested by ulcer index method. Compounds with electron attracting substituents such as 2c and 2e were found to be promising in terms of the ratio of efficacy and adverse effect. These compounds generally exhibited better activity than those of earlier series signifying fluorine substitution.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Croton Oil; Edema; Female; Fluorine; Male; Mannich Bases; Mice; Pain; Pain Measurement; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Structure-Activity Relationship; Sydnones

A series of 4-[(4-aryl)methylidene]amino-2-(substituted-4-ylmethyl)-5-{1-[4-(2-methylpropyl)phenyl]ethyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione (6) were synthesized from an arylpropionic acid namely, ibuprofen by a three-component Mannich reaction. Aminomethylation of 4-[(4-aryl)methylidene]amino-5-{1-[4-(2-methylpropyl)phenyl] ethyl}-4H-1,2,4-triazole-3-thiol (5) with formaldehyde and a secondary amine furnished this novel series of Mannich bases (6). Both Schiff bases (5) and Mannich bases (6) were well characterized on the basis of IR, NMR, mass spectral data and elemental analysis. They were screened for their anti-inflammatory, analgesic, antibacterial and antifungal activities. Some of the Mannich bases (6) carrying morpholino and N-methylpiperazino residues were found to be promising anti-inflammatory and analgesic agents.

Topics: Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspergillus; Edema; Escherichia coli; Ibuprofen; Inflammation; Mannich Bases; Mice; Pain; Rats; Rats, Wistar; Schiff Bases; Staphylococcus aureus; Triazoles

Some novel Mannich base isatin derivatives were synthesized by reacting 1-(5-methyl-2-oxoindolin-3-ylidene)-4-(substitutedpyridin-2-yl)thiosemicarbazide with formaldehyde and several secondary amines. Their chemical structure was elucidated by means of spectral (FT-IR, (1)H- and (13)C-NMR and mass) analysis. Investigation of anti-inflammatory activity of synthesized compounds was done by carrageenan induced paw oedema method using diclofenac sodium as standard drug and analgesic activity was done by acetic acid induced writhing method. The synthesized compounds showed significant anti-inflammatory and analgesic activity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Chemical Phenomena; Chemistry, Physical; Edema; Female; Formaldehyde; Indicators and Reagents; Indoles; Isatin; Magnetic Resonance Spectroscopy; Male; Mannich Bases; Mass Spectrometry; Pain Measurement; Rats; Spectrophotometry, Infrared; Thiosemicarbazones

Chalcones and Mannich bases have been reported to present antiinflammatory activities as well as inhibitory activities on several factors implicated in inflammation disorders. A series of chalcones and some related Mannich bases were prepared by Claisen-Schmidt condensation of appropriate acetophenones with appropriate aromatic aldehyde. Mannich bases were derived from chalcones, with formaldehyde and the corresponding amine. The compounds were tested in vitro for their ability to inhibit various enzymes involved in the arachidonic acid cascade, for their antioxidant behaviour and in vivo for anti-inflammatory activity. Some chalcones and Mannich bases present strong anti-inflammatory and antioxidant activities. Almost all the tested compounds present high inhibitory activity on lipid peroxidation. Some compounds showed potent inhibitory effect on superoxide anion formation. Among the tested compounds 5 and 6 showed the highest lipoxygenase (LO) inhibitory activity. All the tested compounds inhibit both the proteolytic and esteratic activities of trypsin and chymotrypsin. The results indicated that the anti-inflammatory effects of the compounds were partially mediated, through their antioxidant activity. Attempts to correlate quantitatively structure with activity revealed that lipophilicity and molar refractivity influence the biological response.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Biphenyl Compounds; Carrageenan; Chalcones; Chymotrypsin; Edema; Esterases; Free Radical Scavengers; Glutathione; Heme; Indicators and Reagents; Lipids; Magnetic Resonance Spectroscopy; Mannich Bases; Picrates; Reactive Oxygen Species; Spectroscopy, Fourier Transform Infrared; Superoxides

A series of 2-[[4-(substituted-phenyl/ benzyl)-1-piperazinyllmethyl]-6-(4-methoxyphenyl)-3(2H)pyridazinone derivatives was prepared and examined for analgesic and anti-inflammatory activities. The structures of these new pyridazinone derivatives were confirmed by their IR and 1H-NMR spectra and elementary analysis. Among the compounds prepared, 2-[[4-(4-fluorophenyl)-1-piperazinyl]methyl]-6-(4-methoxyphenyl)-3(2H)pyridazinone IVe was found to be a most promising analgesic and anti-inflammatory agent. Compound IVe showed more potent analgesic activity than acetylsalicyclic acid in the phenylbenzoquinone-induced writhing test. Also IVe showed anti-inflammatory activity comparable to that of the standard compound indometacin against the carrageenan-induced paw edema. Side effects of the compounds were examined on gastric mucosa. None of the compounds showed a gastric ulcerogenic effect compared with reference nonsteroidal anti-inflammatory drugs. On the basis of the available data, the structure-activity relationship of the series of 2-[[4-(substituted-phenyl/benzyl)-1-piperazinyl]methyl]-6-(4-methoxyphenyl)-3(2H) pyridazinones is also discussed.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzoquinones; Edema; Foot; Indicators and Reagents; Magnetic Resonance Spectroscopy; Male; Mannich Bases; Mice; Muscle Contraction; Pyridazines; Solvents; Spectrophotometry, Infrared; Stomach Ulcer; Structure-Activity Relationship

The synthesis of several coumarin Mannich bases is described. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. Their lipophilicity was determined experimentally by RPTLC method. All compounds were evaluated for their antiinflammatory and antioxidant activity and for their ability to inhibit in vitro lipoxygenase. The derivatives were found to present antioxidant and antiinflammatory activities. The tested derivatives inhibited carraggeenin-induced hind paw edema. They also significantly suppressed the arthritis induced by Freund's adjuvant. Compound 10, the most active in vivo, was found to possess protective properties against adjuvant-induced arthritis in rats. The biological in vitro activities were concentration dependent. Hydrophilicity, the presence of a free 7-OH, and steric requirements for the substituent at position 8 are the most important factors in terms of SAR. An attempt was made to correlate several physicochemical properties of the molecules with their in vivo/in vitro activity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Carrageenan; Coumarins; Cyclooxygenase Inhibitors; Edema; Female; Free Radical Scavengers; Immunologic Factors; Lipoxygenase Inhibitors; Male; Mannich Bases; Rats; Rats, Inbred F344; Structure-Activity Relationship; Superoxides

Seventeen novel resveratrol derivatives were synthesized. Their anti-inflammatory activities were tested on xylene-induced mouse ear edema. The pharmacological results showed that some compounds have potent anti-inflammatory activities.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzene Derivatives; Ear, External; Edema; Indicators and Reagents; Mannich Bases; Mice; Pyridines; Resveratrol; Spectrometry, Mass, Electrospray Ionization; Stilbenes

Schiff bases and phenyl hydrazone of isatins were prepared by reacting isatin and the appropriate aromatic primary amine/hydrazines. A new series of the corresponding N-mannich bases were synthesized by reacting them with formaldehyde and diphenylamine. The chemical structures were confirmed by means of their 1H-NMR, IR spectral data and elemental analysis. The compounds were screened for analgesic, antiinflammatory and antipyretic activity. 1-Diphenylaminomethyl-3-(1-naphthylimino)-1,3-dihydroindol-3-one (4), 3-(1-naphthylimino)-5-bromo-1,3-dihydroindol-2-one (2) and 1-diphenylaminomethyl-3-(4-methylphenylimino)-1,3-dihydroindol-3-one (7) were found to exhibit the highest analgesic, anti-inflammatory and antipyretic activity respectively. 1-Diphenylaminomethyl-3-(4-methylphenylimino)-1,3-dihydroindol-3-one (7) was found to be the most active compound of the series.

Topics: Acetic Acid; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chromatography, Thin Layer; Edema; Female; Fever; Hydrazones; Isatin; Magnetic Resonance Spectroscopy; Male; Mannich Bases; Mice; Schiff Bases; Spectrophotometry, Infrared

Fourty-three new benzoxazolinone derivatives having a piperazinomethyl group at the third position of the ring were synthesized by using appropriate benzoxazolinones and 4-substituted piperazines via a Mannich reaction. The structures of the compounds were elucidated by spectral data and microanalyses. Analgesic activities were evaluated by a modified Koster test. All compounds, except 7, 14, 21, 32, and 41, showed analgesic activity higher than that of acetylsalicylic acid. The compounds were also screened for their anti-inflammatory activity using a carrageenan paw edema test, and those exhibiting high anti-inflammatory activity were investigated for their ability to inhibit prostaglandin E2 induced paw edema. The results of anti-inflammatory testing indicated that most of the compounds were more active than indometacin. Ulcerogenic activities of the compounds were also studied and no gastrointestinal bleeding was observed at the 100 mg/kg dose level.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Benzoxazoles; Carrageenan; Edema; Female; Mannich Bases; Mice; Piperazines; Prostaglandin Antagonists; Stomach Ulcer