Anti-inflammatory properties of 4,5-diphenyl-2-oxazolepropionic acid (oxaprozin)

Abstract

The uxazole, oxaprozin has a spectrum of activity in various in vivo and in vitro, chronic and acute inflammatory models in 3 species indicating that it belongs to the general class of non-steruidal anti-inflammatory agents. Possible advantageous features of oxaprozin over existing nonsteroidal anti-inflammatory agents include relative safety, minimal irritant properties on the gastrointestinal tract, long half-life, and urieosurie properties.

Oxaprozin-Loaded Lipid Nanoparticles towards Overcoming NSAIDs Side-Effects

“…The micrographs shown also particles with sizes slightly different from those obtained by DLS. Though, most of the particles, primarily from the functionalized oxaprozin loaded NLC (the formulation of interest) demonstrated sizes 38 superior to 200 nm which is the minimum size pretended for our particles. Diameter differences between TEM and DLS analysis can be justified by the fact that DLS analyses the hydrodynamic radius.…”

“…(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].…”

“…Oxaprozin highly binds to plasma proteins (99.9%) with high affinity what leads to a long plasma elimination with a half-life of 50 to 60 hours. This elevated duration of action allows the administration of a single oxaprozin dose per day of 600 to 1800 mg [32,39,40,42,43].…”

Structural diversity of selective COX-2 inhibitors

“…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].…”

Design, Synthesis, and in-Vivo Evaluation of 4,5-Diaryloxazole as Novel Nonsteroidal Anti-inflammatory Drug

“…Oxaprozin ( Fig.1) possesses a longer-term effect and lower GI toxicity than other NSAIDs, 6,7) but its poor selectivity, high dose, and long half-life greatly limit its clinical use. 8,9) Puig et al have studied a series of 3,4-diaryloxazole derivatives, the results show that when the benzene ring has the substituent of 4-methylsulfonyl or 4-aminosulfonyl, the derivatives possess anti-inflammatory and analgesic activities, at the same time, the fluoro substitutes on the benzene ring, the potency has increased 3 times compared with the nonsubstituted derivatives.…”