Effect of structural change on acute toxicity and antiinflammatory activity in a series of imidazothiazoles and thiazolobenzimidazoles

Powers, Larry J.; Fogt, S. W.; Ariyan, Z. S.; Rippin, D. J.; Heilman, Richard D.; Matthews, Richard J.

doi:10.1021/jm00137a022

Cited by 32 publications

(14 citation statements)

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“…Arthritis was induced in rats using the method of Powers[12] with slight modification. Briefly, on day 0, after an initial measurement of paw volume, 0.1 ml CFA was injected into the right hind paw.…”

Section: Methodsmentioning

confidence: 99%

Novel 2,5-disubstituted-1,3,4-oxadiazoles as anti-inflammatory drugs

et al. 2014

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Objective:1,3,4-oxadiazole ring is a versatile moiety with a wide range of pharmacological properties. The present work deals with the synthesis and evaluation of the anti-inflammatory activity of two novel 2,5-disubstituted-1,3,4-oxadiazoles (OSD and OPD).Materials and Methods:Carrageenan-induced rat hind paw edema was employed as an acute model of inflammation. For evaluating sub-acute anti-inflammatory activity, carrageenan-induced inflammation in rat air pouch was employed. Complete Freund's adjuvant-induced arthritis in rats was used as a model of chronic inflammation. To evaluate in vitro anti-inflammatory activity, lipopolysaccharide (LPS)-stimulated RAW264.7 cells were used.Results:OSD (100 mg/kg) reduced carrageen-induced paw edema by 60%, and OPD (100 mg/kg) produced a modest 32.5% reduction. OSD also reduced leukocyte influx and myeloperoxidase in carrageenan-induced rat air pouch model. In complete Freund's adjuvant-induced arthritis model, both OSD and OPD (200 mg/kg for 14 days) reduced paw edema and NO levels. In LPS-stimulated RAW264.7 cells, OSD and OPD inhibited formation of nitric oxide and reactive oxygen species, with OPD showing a better activity in comparison to OSD.Conclusions:OSD was the better of the two compounds in in vivo models of inflammation. The o-phenol substitution at position 2 of oxadiazole ring in OSD may be responsible for its better in vivo anti-inflammatory activity. The ability of the compounds to inhibit LPS-induced pro-inflammatory mediator release suggests an anti-inflammatory mechanism targeting LPS-TLR4-NF-κB signalling pathway, which needs to be explored in detail. The disparate efficacy in vitro and in vivo also requires in-depth evaluation of the pharmacokinetics of these novel oxadiazoles.

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Section: Methodsmentioning

confidence: 99%

Novel 2,5-disubstituted-1,3,4-oxadiazoles as anti-inflammatory drugs

et al. 2014

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“…1,3,4 Compound was prepared from N-(4-fluorophenyl)-3-oxobutanamide (10 mmol, 1.9 g of the crude product). 1,3,4 Compound was prepared from N-(4-fluorophenyl)-3-oxobutanamide (10 mmol, 1.9 g of the crude product).…”

Section: Methodsmentioning

confidence: 99%

“…The synthesis of 1e was based on refs. 1,3,4 Compound was prepared from N-(4-fluorophenyl)-3-oxobutanamide (10 mmol, 1.9 g of the crude product). Yield 0.9 g (40 %), white needles; m.p.…”

Section: Methodsmentioning

confidence: 99%

“…1 We are interested in structural aspects of this class of compounds particularly with respect to intra-and intermolecular hydrogen bonding. 1,3,4 N-Aryl-3-oxobutanamides have been obtained from substituted anilines and ethyl acetoacetate by the ester-amine method. 2 We have synthesised derivatives 1b-e by chlorination of N-aryl-3-oxobutanamides with sulfuryl chloride in toluene.…”

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confidence: 99%

“…2 We have synthesised derivatives 1b-e by chlorination of N-aryl-3-oxobutanamides with sulfuryl chloride in toluene. 1,3,4 N-Aryl-3-oxobutanamides have been obtained from substituted anilines and ethyl acetoacetate by the ester-amine method. 5 The characterisation of derivatives 1b-d corresponds to literature data.…”

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confidence: 99%

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