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Sixteen 1-(1-naphthyloxy)acetyl-4-substituted-3-thiosemicarbazides, 2-substituted amino-5-(1-naphthyloxy)methyl-1,3,4-oxadiazoles, 2-substitutedamino-5-(1-naphthyloxy) methyl-1,3,4-thiadiazoles and 3-(1-naphthyloxy)methyl-4-substituted-1,2,4-triazole-5-thiones were synthesized. The structures of the compounds have been elucidated by UV, IR, 1H-NMR, 13C-NMR spectra and elemental analysis. The anti-inflammatory activities of the compounds were evaluated by carregeenan induced hind paw edema and air-pouch inflammation tests in mice. In carrageenan induced hind paw edema test, compounds 1a, 1d, 3d, 4a showed equivalent or higher activity compared to naproxen and phenylbutazone. In the air-pouch inflammatory model, compounds 1a, 1b, 1d, 2c, 3c, 3d, 4a and 4d showed marked anti-inflammatory activity. The ED50 values of these compounds ranged between 24-36 mg/kg. Side effects of the compounds on gastrointestinal system and kidneys were examined and none of the compound showed significant side effects.

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New 4-arylhydrazono-3-methoxymethyl-2-pyrazolin-5-ones (5a-j) and 4-arylhydrazono-3-methoxymethyl-1-phenyl-2-pyrazolin-5-ones (6a-j) were synthesized by the reaction of ten novel methyl 2-arylhydrazono-4-methoxy-3-oxobutanoates (4a-j) with hydrazine hydrate and phenylhydrazine, respectively. Treatment of 5a with acetic anhydride yielded 1-acetyl-4-arylhydrazono-3-methoxymethyl-2-pyrazolin-5-one (7). The structures of the tautomerically dynamic compounds were established by spectral data (IR, 1H-NMR, 13C-NMR, EIMS and CIMS) and elemental analysis. The analgesic activity of the title compounds was determined by the modified Koster's test. The most active compound was 4-[(4-chlorophenyl)hydrazono]-3-methoxymethyl-1-phenyl-2-pyrazolin-5-one (6c) demonstrating twice the activity (60%) exerted by the reference drug acetylsalicylic acid (ASA, 27%). The majority of the tested compounds were found to be more effective than ASA.

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In this study, the synthesis of some new 2-thioxo-1,2,3,4-tetrahydropyrimidines and their condensed derivatives, thiazolo[3,2-a]pyrimidines, are described. The structures of the compounds were confirmed by 1R, 1H-NMR, 13C-NMR, and mass spectroscopy. The direct high-performance liquid chromatographic separation of the compounds on derivatized cellulose chiral stationary phases such as cellulose tris(3,5-dimethylphenylcarbamate) (OD), cellulose tris(4-methylphenylcarbamate) (OG), and cellulose tris(4-methylbenzoate) (OJ) was studied. All of the compounds were screened for their antiinflammatory activity and also investigated histopathologically. Compounds 3 and 1a were found to be the most promising antiinflammatory agents in this group.

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Sixteen new 2-benzylidene-7-methyl-3-oxo-5-(substituted phenyl)-2, 3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid methyl esters (1a-4d) have been synthesized by reacting 1,2,3,4-tetrahydropyrimidine-2-thiones (1-4) with chloroacetic acid and appropriate benzaldehydes in a single step. Their structures have been proved by IR, 1H NMR, mass spectra and elemental analysis. The compounds were tested for their anti-inflammatory activities. Test results revealed that compounds 1b, 1c, 4a and 4c exerted moderate anti-inflammatory activity at the 100 mg/kg dose level compared with indomethacin.

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Twelve new 3-[2-(2- and/or 4-pyridyl)ethyl]benzoxazolinone derivatives have been synthesized by reacting 2- and/or 4-vinylpyridine and appropriate benzoxazolinones. Their chemical structures have been proven by IR, 1H-NMR and elemental analysis. Analgesic activities of these compounds were investigated by a modified Koster and constant temperature hot-plate test. Test results revealed that most of the compounds at 100 mg/kg dose level showed significant analgesic activities when compared to acetylsalicylic acid and morphine. Therefore the compounds were screened for their anti-inflammatory activities using the carrageenan hind paw edema test. Compounds 3-8 were found more active than indometacin. In gastric ulceration studies, any of the compounds showed no gastrointestinal bleeding at 100 mg/kg dose level.

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Ten new benzoxazolinone derivatives having a disubstituted benzoyl group at the six position of the ring were synthesized by reacting 2-benzoxazolinone with aromatic carboxylic acids in the presence of polyphosphoric acid. The structure of the compounds were elucidated by IR, 1H NMR, MS and elemental analysis. Analgesic activity was evaluated by a modified Koster test. Seven compounds showed analgesic activities higher than that of acetylsalicylic acid.

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Twenty-two new 3-[2-(2-and/or 4-pyridyl)ethyl]benzoxazolinone and oxazolo[4,5-b]pyridin-2-one derivatives have been synthesized by reacting 2- and/or 4-vinylpyridine and appropriate benzoxazolinones and oxazolo[4,5-b]pyridine-2-one. Their chemical structures have been proven by IR. 1H-NMR, 13C-NMR, mass spectroscopy, and elemental analysis. The analgesic activities of these compounds were investigated by a modified Koster's Test. Test results revealed that, at 100 mg/kg dose level, most of the compounds showed significant analgesic activities when compared to aspirin. Therefore the compounds were screened for their antiinflammatory activities using the carrageenan hind paw edema test. Compounds 1, 7, 10, 11, 12, 13, 15, 18, 20, 21 were found more active than indomethacine. In gastric ulceration studies gastrointestinal bleeding was not observed at 100 mg/kg dose level in compounds 1 and 2.

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Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones (4-10) were obtained in a one step synthesis by heating 3-aryl-5-mercapto-1,2,4-triazoles (3a-d) with chloroacetic acid and appropriate aromatic aldehyde in acetic acid and acetic anhydride in the presence of anhydrous NaOAc. Michael type addition of cyclic secondary amines (N-methylpiperazine, piperidine) to 4-10 gave 2-phenyl-6-(alpha-aminoarylmethyl)thiazolo[3,2-b]-1,2,4-triazole-5 -ols (4a-10b). The structures of the compounds were confirmed by spectral and elementary analysis. The compounds synthesized in previous and present studies were investigated for their anti-inflammatory activities.

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In this study, thirty six new 2-benzylidene-7-methyl-3-oxo-5- phenyl-2,3-dihydro-5H-thiazolo[3,2-alpha]pyrimidine-6-carboxylic acid methyl esters were synthesized and characterized by spectral, crystallographic, and elemental analysis. The antiinflammatory activity of the compounds was tested by the carrageenan hind paw edema test. It was found that compound 6a having a 2-meth-oxyphenyl group at position 5 and a benzylidene group at position 2 was the most potent compound in this series. All the compounds that were tested for ulcer activity gave positive results.

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Six saponins, cyclaminorin (1), deglucocyclamin (2), cyclacoumin (3), cyclamin (4), isocyclamin (5), and mirabilin (6) were isolated from the tubers of Cyclamen mirabile. Compound 6 is a new natural compound, and its structure was established as 3-[O-beta-[[beta-D-xylopyranosyl-(1-->2)]- [beta-D-glycopyranosyl-(1-->6)]-beta-D-glucopyranosyl-(1-->4)]-[be ta-D- glucopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl]-3 beta,16 alpha,28-trihydroxyolean-12-en-30-oic acid (6). The structure elucidation of this compound was accomplished using both spectral and chemical methods. Antimicrobial and uterocontractile activities of the saponins were also investigated.

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In this study, the synthesis and analgesic activities of some new 6-acyl-3-(4-substituted benzoylmethyl)-2-benzoxazolinone derivatives are reported. Their structures were confirmed by microanalysis, IR, and NMR spectral analysis. The obtained compounds were screened for their analgesic activities. Analgesic activity of these compounds was investigated by modified Koster Test. The 11 compounds synthesized showed good analgesic activities.

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Ketoprofen (KP) is a potent non-steroidal anti-inflammatory drug which is used for the treatment of rheumatoid arthritis. The oral administration of KP can cause gastric irritation and renal adverse effects. Topical application of the drug can bypass gastrointestinal disturbances and provide relatively consistent drug levels at the site of action. Since the efficacy of an ointment depends on the type of ointment base and the concentration of the drug, four different bases (white petrolatum, cold cream, hydrophilic ointment and Carbopol 940 gel) were used at 1, 3, 5, 7 and 10% concentrations of KP to evaluate the effect of ointment base and concentration. The general rank order of the drug release was found to be: Carbopol gel > hydrophilic ointment > cold cream > white petrolatum. There was a positive correlation between the concentration of KP and release rate for all bases except Carbopol gel. The in vivo percutaneous absorption of KP from different ointment bases at 3% concentration was studied by carrageenan-induced paw edema in mice. The rank order of the percent edema inhibition was as follows: Carbopol gel > or = hydrophilic ointment > cold cream > white petrolatum. There was a good correlation between the in vitro and in vivo results.

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The protective effect of L-arginine against reactive oxygen species-induced impairment of endothelium-dependent vasorelaxation was investigated in isolated ring preparations of rat aorta. The aortic rings were subjected to reactive oxygen species generated by the electrolysis of the bathing solution or incubation with H2O2. Endothelium-dependent relaxation in response to acetylcholine of precontracted aortic rings was attenuated when the rings were exposed to reactive oxygen species or H2O2. Incubation prior to electrolysis with either L-arginine, the endogenous precursor of nitric oxide (NO), or sodium nitroprusside, an exogenous donor of NO, protected the aortic rings against the impairment of endothelium-dependent relaxation. However, D-arginine and glycine, amino acids which do not produce NO, also afforded protection in this model. Therefore, not only the increased synthesis of NO but also the oxidation of L-arginine, with concomitant disproportionation of reactive oxygen species, may be responsible for the protective effect against reactive oxygen species-induced loss of the endothelial response to acetylcholine in isolated rat aorta.

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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.

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Some new 2,3-dihydro-3-hydroxy-6-phenyl-3-(4-substituted- (phenylthiazolo[3,2-b][1,2,4]triazole derivatives were synthesized as antifungal agents. After their structures were confirmed by microanalysis and IR and NMR spectral analysis, their antifungal activities against Candida albicans, Candida parapsilosis, Candida stellatoidea, and Candida pseudotropicalis were investigated. Contrary to our expectations, all proved to have poor antifungal activities. Because 2,4-dihydro-3H-1,2,4-triazol-3-ones are a new class of anticonvulsant agents, a series of thiazolo[3,2-b][1,2,4]triazoles was evaluated for anticonvulsant activity and observed as potential anticonvulsant candidates. All compounds examined exhibited activity against both maximal electroshock and pentylene tetrazole-induced seizures in mice.

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Sixteen new ethanone and ethanol derivatives of 6-acyl-2-benzoxazolinones were synthesized and their chemical structures elucidated by IR, 1H-NMR and elemental analysis. Analgesic activities of these compounds were investigated by modified Koster test and constant temperature hot plate test. All the compounds showed higher analgesic activity than aspirin. Therefore the compounds were tested for their antiinflammatory activities using the carrageenan hind-paw edema test. All the compounds that showed high antiinflammatory activity were then further assayed for their ability to inhibit prostaglandin E2 (PGE2) induced paw edema. None of the compounds induced gastric ulceration.

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6-Acetyl-2(3H)-benzoxazolone derivatives were reacted with appropriate piperidine derivatives and formaldehyde in methanol to give the corresponding 6-acyl-3-piperidinomethyl-2(3H)-benzoxazolones. The obtained compounds were screened for their analgesic and antiinflammatory activities. Analgesic activity of these compounds was investigated by modified Koster test. Antiinflammatory activity was assayed by using carrageenan induced mouse paw edema test and arachidonic acid edema. The 15 compounds synthesized showed good analgesic activities; compounds 1,3 and 6 moved to be active inhibitors of edema.

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In the present study, aluminum (Al) accumulation has been examined after aluminum loading in mice. The kidney, liver, and brain aluminum levels for mice that had been treated orally with aluminum hydroxide for 105 d and for the control group were determined using graphite furnace atomic absorption spectrophotometry (GFAAS) following an acid digestion. Matrix modifier consisted of 2% Triton X-100 and 2% Mg (NO3)2. Al loaded mice showed a significant increase in tissue aluminum levels, relative to the control group.

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6-Acyl-2(3H)-benzoxazolone derivatives were reacted with 4-substituted phenacyl bromide in ethanol to give the corresponding 6-acyl-3-[(4-substitutedbenzoyl)methyl]-2(3H)-benzoxazolones . The compounds were screened for their analgesic, antiinflammatory activities. The eight compounds synthesized showed high analgesic activities and further investigation revealed compounds 3, 6 and 7 to be potent inhibitors of carrageenan- and arachidonic acid-induced paw edema. The PGE2 isolated from the carrageenan paw edema fluid was also significantly low in mice treated with compounds 3, 6 and 7.

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