Oxaprozin: Synthesis, SAR study, physico-chemical characteristics and pharmacology

Oxaprozin (3-(4,5-diphenyloxazol-2-yl)propanoic acid) is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of numerous inflammatory musculoskeletal diseases, including rheumatoid arthritis, osteoarthritis, tendonitis, ankylosing spondylitis and bursitis. It is the first representative member of the diaryl- substituted heterocyclic compounds, which have found clinical use as selective cyclooxygenase-2 (COX-2) inhibitors. The U.S. Food and Drug Administration (FDA) approved its official use in 1992. Both the anti-inflammatory and analgesic properties of oxaprozin are mainly due to the potent inhibition of COX. However, oxaprozin-induced benefits might be also regulated by other COX-independent pathways. It has been shown that oxaprozin induced direct proapoptotic effects in CD40L-treated human monocytes independently of COX inhibition. It also has several advantages in the treatment of inflammatory diseases in comparison to other NSAIDs such as aspirin, naproxen, indomethacin and phenylbutazone, which enabled oxaprozin to become one of the most used NSAIDs in America. Oxaprozin, as other members of the group of NSAIDs, can cause gastrointestinal complications, but significantly lower due to relatively high pKa value. In this paper, the importance of oxaprozin in the treatment of arthritis and its pharmacokinetic properties were described, therewith its activity and side effects were compared with other commercially available anti-inflammatory drugs.Oksaprozin (3-(4,5-difeniloksazol-2-il)propanska kiselina) jeste nesteroidni anti-inflamatorni agens koji se koristi za simptomatsko lečenje inflamacije, bola i reumatoidnih oboljenja. U ovom radu prikazani su različiti postupci dobijanja oksaprozina, njegovih derivata i detaljan opis mehanizma reakcija sinteze, kao i njegova fizička i hemijska svojstva. Pored osnovnih molekulskih osobina koje su značajne za aktivnost oksaprozina kao nesteroidnog anti-inflamatornog leka, navedeni su najznačajniji podaci SAR (eng. Structure-Activity Relationship) studije sintetisanih njegovih analoga. Istaknut je značaj oksaprozina u lečenju artritisa, njegova farmakokinetička svojstva i poređena je njegava aktivnost i sporedni efekti sa ostalim komercijalno dostupnim anti-inflamatornim lekovima

Lipophilicity assessment of some 5,5-disubstituted hydantoins by the means of reversed phase liquid chromatography

The retention of some 5,5-disubstituted hydantoins was investigated by reversed phase high performance thin-layer chromatography (RP HPTLC) and reversed phase high-pressure liquid chromatography (RP HPLC). The mobile phases were mixtures of methanol-water and acetonitrile-water in various volume fractions. In order to explore and visualize similarities and differences among the investigated compounds and chromatographic system, Principal Component Analysis (PCA) was used. Results show that the experimental lipophilicity indices estimated from retention data (Rm,w, log kw) and PC1 are directly correlated with logP values at a high significant statistical level.Ispitano је retenciono ponašanje derivata 5,5-disupstituisanih hidantoina primenom dve tehnike tečne hromatografje na obrnutim fazama, i to hromatografije na tankom sloju velike moći razdvajanja (HPTLC) i tečne hromatografije pod visokim pritiskom (HPLC). Као pokretne faze Korišćene su smeše metanol-voda i acetonitril-voda u različitim zapreminskim odnosima. Da bi ispitali i vizuelno utvrdili sličnosti i razlike među ispitivanim supstancama u korišćenim hromatografskim sistemima, primenjena je analiza glavnih komponenti (PCA analiza). Rezultati su pokazali da između računskih logP vrednosti i hromatografskih parametara lipofilnosti koji su dobijeni ekstrapolacijom retencionih podataka (Rm,w, log kw), као i PC 1 postoji značajna startistička povezanost

Electrochemical Characterization of Oxaprozin on Bare Gold Electrode and Electrode Modified with Bovine Serum Albumin

As the very first electrochemical investigation of oxaprozin, nonsteroidal anti-inflammatory drug, using cyclic voltammetry on gold electrode in 0.05 mol dm(-3) NaHCO3, the synthesized drug, its analytical standard and its content in Duraprox (R) tablets were characterized with one oxidation reaction and the three reduction reactions. All they exhibited the linear concentration dependency of anodic currents at 0.83V for the analytical standard and 0.85V for Duraprox (R) tablets in the range of concentrations 8.44 - 32.78x10(-6) mol dm(-3). The strong adsorption of bovine serum albumin (BSA) on gold electrode in 0.1 mol dm(-3) phosphate buffer solution (pH 7.4) is shown and concentration dependency of anodic currents of oxaprozin standard on BSA/Au is studied. Following the Langmuir adsorption thermodynamic equation, the binding constants of oxaprozin on BSA/Au electrode was calculated with the results 1.23x10(5) dm(3) mol(-1)