Ibuprofen compounds

Considerable advances in asymmetric hydroformylation, a process which, among other things, provides a potential route to enantiomericaHy pure biologically active compounds, have occurred. Of particular interest are preparations of nonsteroidal antiinflammatory (NSAI) pharmaceuticals such as Naproxen (8) and Ibuprofen (9), where the represents a chiral center. 

Nonsteroidal Antiinflammatory Drugs. Nonsteroidal antiinflammatory dmgs (NSAIDs) include, among the numerous agents of this class, aspirin (acetylsaflcyhc acid), the arylacetic acids indomethacin and sulindac, and the arylpropionic acids, (5)-(147) and (R)-(148) ibuprofen, (5)-(149) and (R)- (150), flurbiprofen naproxen (41), and fenoprofen (see Analgesics, antipyretics, and antiinflammatory agents Salicylic acid and related compounds). 

The aluminum salts of dmgs are significant for two principal reasons reduction of dmg acidity in the stomach lining and reduction of undeskable flavor. Examples are the aluminum salts of glycine, acetylsahcyhc acid, ibuprofen, flurbiprofen, fenoprofen, flufenamic acid, oxaprozin, and a variety of aminobenzoic acid. Some of these compounds are Hsted in Table 2. 

AGP columns have wide appHcation for the direct separation of enantiomers of many different classes of dmgs, amines, acids, and nonprotolytic compounds (18,23). Acidic dmgs resolved include ibuprofen [15687-27-17, C 2H g02, ketoprofen [22071 -15 ] and naproxen [22204-53-17,... 

The enantioselectivity a is defined as the distribution ratio of one single enantiomer over the two chiral phases and has been determined experimentally for a variety of compounds (Table 5-1). It has been known from work by Prelog [66, 67] that tartaric acid derivatives show selectivities towards a-hydroxyamines and amino acids. However, from Table 5-1 it is obvious that tartaric acid derivatives show selectivity for many other compounds, including various amino bases (e.g. mirtazapine (10)) and acids (e.g. ibuprofen (11)). The use of other chiral selectors (e.g. PLA)... 

This strategy, for the production of (5 )-ibuprofen, is illustrated in Fig. 7-19. Ibuprofen is derivatized to the corresponding sulphonmethyl ester, but only one enantiomer of this compound is converted by a protease to (5 )-ibuprofen [33]. The resulting (5 )-ibuprofen and the unreacted ibuprofen sulphonmethyl ester can be sep-... 

Like aspirin, both ibuprofen and naproxen are relatively simple aromatic compounds containing a side-chain carboxylic acid group. Ibuprofen, sold... 

There are several hundred reported NF-kB inhibitors (see www.nf-kb.org for a complete and updated list). These inhibitors include natural products, chemicals, metabolites, and synthetic compounds. A large majority of these products, in particular commonly used antiinflammatory drugs such as corticosteroids and the nonsteroidal antiinflammatory drugs (NSADDs) aspirin, sulindac, ibuprofen and sulphasalazine, have the ability to partially inhibit NF-kB activity in cell culture. However, the precise mechanism of action and the specific molecular targets of most of these inhibitors remain unclear. 

The hydrolysis of various para-substituted a-methylstyrene oxides was studied using 10 EHs [184]. The hydrolysis of the isobutyl compound with the enzyme from A. niger WHS the key step in the synthesis of (S)-ibuprofen (Figure 6.65). The (R)-diol was recycled via chemical racemization. 

The results showed that the compounds studied with more frequency in the aquatic environment, and of which, logically, there is more information, are the antibiotics, analgesics and anti-inflammatories (like diclofenac, ibuprofen, naproxen, acetylsalicylic acid, and paracetamol), as well as the p-blocker atenolol. In the category of antibiotics, several families are included, like the macrolides (erythromycin), the fluoroquinolones (ofloxacin and ciprofloxacin), sulfonamides (sulfamethoxazole), penicillins (amoxicillin), the metronidazol, and trimethoprim. Other therapeutic groups also widely studied and frequently found in the environmental waters are the lipid regulators (gemfibrozil and bezafibrat), antiepileptic carbamaze-pine, and antidepressants (diazepam, fluoxetine, paroxetine) (see Table 3). 

Hydroformylation has been extensively studied since it produces optically active aldehydes which could be important precursors for pharmaceutical and fine chemical compounds. Thus, asymmetric hydroformylation of styrene (Scheme 27) is a model reaction for the synthesis of ibuprofen or naproxen. Phosphorus ligands were used for this reaction with excellent results, espe-... 

Analysis of ibuprofen, the active ingredient in several over-the-counter pain relievers, shows that it contains 75.7% carbon, 8.8% hydrogen, and 15.5% oxygen. The mass spectrum of ibuprofen shows that its molar mass is less than 210 g/mol. Determine the chemical formula of this compound. 

The mass spectmm of the compound indicates that its moiar mass is iess than 210 g/moi. The moiar mass caicuiated from the empiricai formuia is 206.27 g/moi. This teiis us that the chemicai formuia of ibuprofen is the same as its empiricai formuia. 

The chemicai formuia of ibuprofen shows that this bioiogicaiiy active compound contains simiiar numbers of C, H, and O atoms as does caffeine, another bioiogicaiiy active compound. A baii-and-stick modei of ibuprofen appears in the margin opposite. 

Yamamoto K, Y Ueno, K Otsubo, K Kawakami, K-I Komatsu (1990) production of 5-(+)-ibuprofen from a nitrile compound by Acinetobacter sp. strain AK 226. Appl Environ Microbiol 56 3125-3129. 

FIGURE 2.20 Schematic presentation of the hydrogen-bonded cyclic dimers of enantiomeric antipodes of 2-phenylpropionic acid, Ibuprofen, and Naproxen (the latter two compounds are drugs from the group of profens). 

Anti-inflammatory drugs such as Ibuprofen, acetaminophen, diclofenac, atorvastatin, and hydrochlorthiazide were detected in the highest concentrations in samples from three WWTPs in Spain [93]. These compounds were present in average concentrations from 43 to 117 ng/g, 42 to 103 ng/g, 28 to 75 ng/g, 21 to 65 ng/g, and 29 to 126 ng/g, respectively. 

Recently, with the development of more advanced and sensitive analytical methods, studies on the fate of pharmaceuticals in WWTP have taken into account the analysis of pharmaceuticals sorbed into sludge (Table 4, and references therein). The antiseptics triclocarban and triclosan and the antibiotic ofloxacin have been reported in sludge at concentrations up to 441, 133, and 58 mg kgdw-1, respectively. Compounds such as the anti-inflammatory ibuprofen, the antiepileptic carbamazepine and the antidepressant fluoxetine have also frequently been reported though at lower levels (11,6 and 3 mg kgdw 1, respectively), whereas the (3-blockers were found at low... 

In order to determine more precisely the fate of pharmaceuticals during sludge treatment, different experiments have been conducted in controlled conditions. In continuous anaerobic reactors treating sludge spiked with pharmaceuticals, Carballa et al. [114] observed removals higher than 80% for naproxen, sulfamethoxazole, and roxithromycin, while 40% and 23% of ibuprofen and iopromide, respectively, were eliminated at both mesophilic (37°C) and thermophilic (55°C) temperatures. For diclofenac and diazepam, elimination of about 60% was observed in mesophilic conditions while in thermophilic conditions, 38% and 73% of these two compounds, respectively, were eliminated. In these experiments, the sludge retention time (15 or 30 days) did not seem to influence pharmaceutical removal... 

For therapeutic drugs, the highest concentrations in the raw sludge corresponded to the analgesics diclofenac (209 ng g ) and ibuprofen (135 ng g-1), and the sulfonamide antibiotic sulfathiazole (143.0 ng g-1). Next in abundance were the diuretic compounds furosemide (79.9 ng g-1) and hydrochlorothiazide (41.3 ng g-1), and the analgesic ketoprofen (42.4 ng g-1). The remaining PhC were found at concentrations below 40 ng g The list of the 24 detected... 

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