Diaryloxazole and Diarylthiazolealkanoic Acids: Two Novel Series of Non-steroidal Anti-inflammatory Agents

Brown, Kevan; Cavalla, J. F.; Green, David; Wilson, A. B.

doi:10.1038/219164a0

Cited by 55 publications

(16 citation statements)

References 6 publications

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“…(Table 1) is a non-selective COX inhibitor NSAID with effective anti-inflammatory, analgesic and antipyretic effects. These therapeutic activities derive from its capability to inhibit COX-2 [37][38][39][40][41][42]. Oxaprozin has an aliphatic propionic acid function attached to the oxazole as side chain, however contrarily to other propionic acid compounds this doesn't possess a chiral centre [40,42].…”

Section: Chemical Classificationmentioning

confidence: 99%

Oxaprozin-Loaded Lipid Nanoparticles towards Overcoming NSAIDs Side-Effects

et al. 2015

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Section: Chemical Classificationmentioning

confidence: 99%

Oxaprozin-Loaded Lipid Nanoparticles towards Overcoming NSAIDs Side-Effects

et al. 2015

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“…The exceptional anti-inflammatory properties of phenylbutazone [24] undoubtedly provided much of the impetus that led chemists to exploit this type of structure. The discovery of the diphenyloxazole derivative oxaprozin as a clinical candidate for the treatment of inflammation is one example of the utility of the diarylheterocycle scaffold [25,26]. Likewise, the 2,3-diarylindole indoxole was disclosed in the early 1960s as a potent anti-inflammatory agent; however, the drug was suspended from clinical development since it caused photosensitivity in humans [27][28][29].…”

Section: Historical Perspectivementioning

confidence: 99%

Structural diversity of selective COX-2 inhibitors

Marnett

Kalgutkar

2004

COX-2 Inhibitors

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“…Oxaprozin (4,5-diphenyl-2-oxazolepropionic acid, Wy:21,743) has been shown to be effective in reducing inflammation in animal models [ 1,2] as well as to be clinically effective in the reduction of inflammation due to rheumatoid arthritis [3]. JANSSEN et al…”

Section: Introductionmentioning

confidence: 99%

Protein binding and clearance of oxaprozin, a highly bound anti-inflammatory agent

Homon¹,

Fluck²,

Janssen³

et al. 1982

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Conventional dialysis cells were used in initial attempts to determine the binding characteristics of oxaprozin (4,5-diphenyl-2-oxazolepropionic acid, Wy-21,743). Equilibration required dialysis times up to 22 hours at 37 degrees C resulting in deterioration of plasma proteins, which in turn leads to highly variable binding values. In contrast, dialysis with Dianorm cells requires less than 4 hours to reach equilibrium. The configuration of the cell optimizes the contact between the solutes and the membrane and allows for a more efficient mixing and exchanging of the solute. The percentage of unbound drug was linearly related to total drug in human plasma samples to which oxaprozin in clinically relevant concentrations (55-405 micrograms/ml) had been added. Likewise, a linear relationship between total drug concentration and the percentage unbound was observed in specimens from a pharmacokinetic study in healthy volunteers. Clearance of total oxaprozin from plasma correlated with the percentage unbound drug. Thus the higher clearance observed under steady-state conditions (where concentrations are higher than following single dose administration) was caused by a larger unbound fraction available to the elimination sites.

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Diaryloxazole and Diarylthiazolealkanoic Acids: Two Novel Series of Non-steroidal Anti-inflammatory Agents

Cited by 55 publications

References 6 publications

Oxaprozin-Loaded Lipid Nanoparticles towards Overcoming NSAIDs Side-Effects

Oxaprozin-Loaded Lipid Nanoparticles towards Overcoming NSAIDs Side-Effects

Structural diversity of selective COX-2 inhibitors

Protein binding and clearance of oxaprozin, a highly bound anti-inflammatory agent

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