Anti-inflammatory drugs ibuprofen

Castell, J.V, Larrauri, A. and Gomez-Lechon, M.J. (1988). A study of the relative hepatotoxi-city in vitro of the non-steroidal anti-inflammatory drugs ibuprofen, flurbiprofen and butibufen. Xenobiotica 18 737-745. 

Recent advances with other anti-inflammatory drugs, ibuprofen and naproxen, which only work by physically blocking the channel to arachidonic acid, mean that the adverse effect of stomach bleeding can be avoided. 

Analysis of non-steroidal anti-inflammatory drugs (ibuprofen, ketoprofen, naproxen, fenoprofen, flurbiproen, and suprofen) Impurity profiling of ketorolac, a chiral nonsteroidal antiinflammatory drug Impurity profiling of a non-steroidal analgesic drug... 

Similarily, styrene and 4-isobutylstyrene were converted to the corresponding carboxylic acids (Equations 4 and 5) by reaction with CO and H20 in the presence of Pd(tppts)3 and p-CH3C6H4S03H (no organic solvent) at 65°C and 50-140 bar CO (the relatively low temperature is required to suppress polymerization of the substrate). The major products were the branched acids in both cases 90% and 74% with styrene and 4-isobutylstyrene, respectively. In the case of 4-isobutylstyrene the branched acid product is the anti-inflammatory drug ibuprofen. 

The ultimate goal in most industrial research is to develop economically attractive processes or products. The technology of asymmetric hydrogenation of 2-arylacrylic acids is probably most useful for the production of naproxen and S-ibuprofen. Naproxen is currently one of the top ten prescription drugs in the world S-ibuprofen is the active isomer in the popular anti-inflammatory drug ibuprofen. Figures 5 and 6 summarize two commercially feasible processes for the manufacturing of these products. 

Figure 29 Separation of the nonsteroidal anti-inflammatory drugs ibuprofen (peak 1), naproxen (2), ketoprofen (3), and suprofen (4) in anion-exchange CEC mode using a strong anion-exchange monolithic column. Conditions on-column alkylated monolith prepared from mixtures consisting of 8% 2-dimethylaminoethyl methacrylate, 24% 2-hydroxyethyl methacrylate, 8% ethylene dimethacrylate, 20% cyclohexanol, 40% 1-dodecanol UV-initiated polymerization at room temperature for 16 h cfpmode= 1423 nm. Column dimensions inner diameter 0.1 mm, total length 335 mm, effective length 250 mm. Mobile phase 0.4 mol/L acetic acid and 4 mmol/L triethylamine in acetonitrile/methanol (60/40), voltage -25 kV, injection -5 kV for 5 s, temperature 50°C, UV detection at 250 nm. (Reprinted from Ref. 127, with permission.)...

P6-26o A new catalytic pathway for an important intermediate in the production of the nonsteroidal anti-inflammatory drug ibuprofen (e.g., Advil) has been developed/CAer/j. Eng. Set, 51, 10, 1663(1996)]. The pathway involves the hydrogenation of p-isobutyl acetophenone (B) in a solution of methanol containing a HY zeolite catalyst and saturated with hydrogen. The intermediate products are p-isobutylphenyl ithanol (C), p-iscbutylphaiylethylnEtl lether (E) and p-isobutylethyl benzene (F). The reaction scheme is shown below. 

Shah SJ, Bhandarkar SD, Satoskar RS. Drug interaction between chlorpropamide and non-steroidal anti-inflammatory drugs, ibuprofen and phenylbutazone. Int J Clin Pharmacol Ther Toxicol 1984 22(9) 470-2. 

Lipase-catalyzed esterifications of racemic carboxylic acids in SCFs have been studied by several groups. The target in all of these studies was the preparation of optically pure anti-inflammatory drugs ibuprofen and naproxen. Rantakyla and Aaltonen reported the kinetic resolution of racemic ibuprofen by esterification catalyzed by immobilized lipase from Mucor miehei [Eq. (1)] (8,74,75) ... 

Antidepressants selective serotonin reuptake inhibitors, tricyclic antidepressants Antihypertensives felodipine Antibiotics quinolones, isoniazid Bronchodilators albuterol, theophylline Corticosteroids prednisone Dopa agonists levodopa Herbals ma huang, ginseng, ephedra Nonsteroidal anti-inflammatory drugs ibuprofen Stimulants amphetamines, methylphenidate, caffeine, cocaine Sympathomimetics pseudoephedrine Thyroid hormones levothyroxine Toxicity anticholinergics, antihistamines, digoxin Withdrawal alcohol, sedatives... 

Nonsteroidal anti-inflammatory drugs ibuprofen, ketoprofen, naproxen sodium Alternative mefenamic acid, acupuncture Bloating/fluid retention Sodium reduction/restriction Spironolactone... 

In a similar manner, the asymmetric hydrogenation of isobutylatropic acid to afford the anti-inflammatory drug ibuprofen has been carried out (Scheme 5.4-2). Here, the reaction was carried out in a [BMIM][PF(l]/MeOH mixture, again followed by product extraction with scC02 (see Section 5.2.4.1 for more details on these hydrogenation reactions). 

The anti-inflammatory drug, ibuprofen, exists in two enantiomeric forms which also can be separated on open tubular columns coated with derivatized P-cyclodextrin. An example of the separation of the isomers of ibuprofen is shown in figure 6.15. 

In 2007, Li and List reported the asymmetric hydrogenation of a-arylaldehydes catalysed by [RuCl2(Xyl-BINAP)(DPEN)], providing the corresponding primary alcohols in excellent enantioselectivities and yields, as shown in Scheme 2.40. As an application of this reaction, the biologically active (5)-enantiomer of the non-steroidal anti-inflammatory drug, ibuprofen, could be... 

As a model nonsteroidal anti-inflammatory drug ibuprofen was chosen. It is very effective for the systemic treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. It is almost insoluble in water (1.74 x IQ- mol L ) [30], while its solubility in IPM is 0.160 + O.OlSg mL [31]. As a weak acid (pK = 4.4) its solubility increases with increasing pH. Ibuprofen shows a considerable surface activity [32] that could contribute to its enhanced permeation through biological membranes [33]. The release profiles of tested ME samples are shown in Figure 10.10a. 

Carboxylic acids can he prepared from nitriles by heating with aqueous acid or base by a mechanism that we ll see in Section 15.7. Since nitriles themselves are easily made by Sn2 reaction of a primary or secondary alkyl halide with CN , the two-step sequence of cyanide displacement followed by nitrile hydrolysis is a good way to make a carboxylic acid from an alkyl halide (RBr RC=N RCO2H). Note that the product acid has one more carbon than the starting alkyl halide. An example occurs in one commercial route for the synthesis of the nonsteroidal anti-inflammatory drug ibuprofen. 

The arylation of malonic acid derivatives with ArPb(OAc)3 has been applied to the synthesis of the important anti-inflammatory drug ibuprofen (Scheme 21). ... 

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