Indomethacin confirmation

In a study NSAIDs indomethacin (2-[l-(4-chlorobenzoyl)-5-methoxy-2-methyl-indol-3-yl]acetic acid), acemetacin (l-[p-chlorobenzoyl]-5-methoxy-2-methylindole-3-acetic acid carboxymethyl ester), and etodolac (( )-l,8-diethyl-l,3,4,9-tetrahydropyrano-(3,4-b)indole-l-acetic acid) were tested on different ROS generating systems (Fig. 1). There are some satisfactory results that confirm that the anti-inflammatory activity of these compounds may be also partly due to their ability to scavenge ROS and RNS. The observed effective scavenging activity may contribute to the anti-inflammatory therapeutical effects [92,100]. 

The well known, beneficial influence of non-steroidal anti-inflammatory drugs (NSAID) on the progress of Alzheimer s disease has been confirmed for some NSAID subtypes. The work by Weggen et al. indicates the potential of COX 1 inhibitors (e.g. Diclofenac, Sulindac, Indomethacin, Ibuprofen, but not the most prominent, Aspirin) in PS inhibition [17]. 

Bugianesi and Shen38 accomplished the synthesis of 1-O-indometh-acin-/3-D-glucopyranuronic acid (85), a major urinary metabolite235 of the anti-inflammatory drug indomethacin, by using 18 as the sugar component. Thus, DCC condensation of 18 and indomethacin in tetra-hydrofuran at room temperature, followed by treatment of the product (50% yield) with zinc dust in acetic acid, afforded the zinc salt of 85 its structure was confirmed by conversion into 86, identical by i.r. and H-n.m.r. spectra with an authentic specimen.263... 

Griffin et al. [34] reported a nested, case-control study involving 1799 AKI cases compared to 9899 controls. Chart survey was used to confirm both the diagnosis of AKI and the use of NSAIDs. 18.1% of the AKI patients were NSAID-users compared to only 11.3% of the controls (OR 1.58 1.34-1.86). They estimated that NSAID-use was associated with 25 excess hospitalizations/10, 000 years of use. The NSAIDs with odds ratio that were significantly correlated with AKI included ibuprofen, piroxicam, fenoprofen, and indomethacin. Based on these finding and the results of three other case-control studies, they concluded that the odds ratio significantly favored a direct relationship between NSAID ingestion and AKI, especially in the elderly. 

The pathways of polymorphic transitions for cephalexin, chloramphenicol palmitate, and indomethacin have been studied, and the composition of partially transformed samples determined by XRPD.27 The metastable forms of chloramphenicol palmitate were found to transform into the stable phase when found at room temperature, confirming the results of a previous study.28 In contrast, cephalexin became amorphous upon grinding. Indomethacin exhibited the interesting behavior of becoming amorphous when ground at 4°C, but could be transformed into a metastable phase when ground at 30°C. 

The possible modes of action of indomethacin remain to be a subject of active interest. As a reference compound it has been found to be active in most of the in vitro and in vivo assays mentioned above. While none of these can be considered as the primary mode of action, certainly several are contributory. An earlier report of kallikrein inhibition was not confirmed.The suggestion37 that the antiinflammatory activity of indomethacin may be due to the displacement of tissue-bound corticosteroid has also been disputed. 3 The distribution cind metabolism of indomethacin in various species have been reported in detail39, and a number of long-term clinical studies have been published. 3... 

During endogenous release of thromboxane hi, after provoking the heparin-protamine reaction in awake sheep, Fratacci et a/. (1991) confirmed that inhaled NO can act as a selective pulmonary vasodilator. Significant reduction of the peak pulmonary artery pressure (PAP) required an inhaled NO dose of 180 ppm in this study. Furthermore, after indomethacin blockade of arachidonic acid metabolite production, it was shown that inhaled NO still dilated the lung vasculature (Fratacci etal., 1991). Thus, the vasodilatory effect of NO in sheep is independent of prostacyclin release. 

The solubility parameter values obtained from the simulations were found to be in reasonable agreement with those calculated using the traditional group contribution methods (Table 2.2). Furthermore, the miscibility/immiscibility prediction was experimentally confirmed, since DSC showed melting point depression of PEO with increasing levels of indomethacin and thermal analysis of blends of indomethacin with sucrose and glucose verified general immiscibility. The solubility parameter... 

Raman and IR spectroscopy have both been used extensively in the characterization of salts and co-crystals to identify functional groups corresponding to the individual components, to characterize proton transfer in the solid state and to confirm the presence of new binary phases based on unique IR/Raman fingerprints. Confirmation of the latter is achieved simply through comparison with the pure component spectra, as shown for an indomethacin-saccharin co-crystal in Figure 10.5. In this case, not only were the Raman carbonyl... 

A recently disclosed analog is the 5-dimethylamino derivative (III) with a potency nearly 1/2 x indomethacin but with different metabolic and distribution properties.The tetrazole euialog of indomethacin (IV) is about 1/20 to 1/10 as potent in animals and being investigated in the clinic. The rigid position isomer (V) was found previously to be much less active in animals at Merck Research Laboratories amd this was confirmed independently in France. ... 

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