mannich-bases and Stomach-Ulcer

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 novel series of coumarinyl Mannich bases (3a-1) have been synthesized by reacting 3-acetyl coumarin (1) with various substituted secondary amines (2a-1) in presence of paraformaldehyde. The structures of the newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR and HRMS (high resolution mass spectral) data. Title compounds were screened for in vivo acute anti-inflammatory activity using the carrageenan-induced rat paw edema assay model. Among the compounds tested, 3-[3-(diethylamino)propanoyl]-2H-chromen-2-one (3a)and 3-[3-(piperidine-1-yl) propanoyl]-2H-chromen-2-one (3c) showed 63.1 and 66.7% inhibition, respectively, as compared to the standard drug diclofenac (CAS 15307-86-5, 68.8%). These potent compounds showed encouraging analgesic andantipyretic activities.

Topics: Acetic Acid; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents; Coumarins; Drug Evaluation, Preclinical; Female; Fever; Indicators and Reagents; Magnetic Resonance Spectroscopy; Male; Mannich Bases; Mass Spectrometry; Mice; Pain Measurement; Solvents; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Stomach Ulcer

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

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