Propionic acid derivatives agents

It is by now apparent that the nature of the aryl group in the aryl acetic and aryl propionic acid antiinflammatory agents can be varied quite widely without loss of activity. The corresponding derivatives of homologous xanthones and thioxanthones thus both show activity as nonsteroid antiinflammatory agents. 

Naproxen is a non-steroidal anti-inflammatory agent classified as a propionic acid derivative. 

The analgesic efficacy and safety profiles of the nonsalicylate NSAIDs make them appropriate alternatives to aspirin for treatment of mild to moderate pain. Most NSAIDs are used primarily for their anti-inflammatory effects, but they are also effective analgesics that relieve pain associated with a variety of ocular conditions. The nonsalicylate NSAIDs consist of the propionic acid derivatives, cyclooxygenase-2 (COX-2) inhibitors, and several other less commonly used agents (Table 7-2). 

Carprofen, a propionic acid derivative, is an effective analgesic and weak anti-inflammatory agent. Carprofen contains a chiral center at the C2 of the propionic moiety and, therefore, exists in two stereoisomeric forms, the S(-l-)- and P(-)-enan-tiomers. The approved product for the horse is a racemic mixture of the two antipodes. In the horse the S(+)-form has more rapid clearance, as a result of selective glucuronidation and subsequent biliary excretion of that enantiomer (Soraci et al 1995). Unlike many NSAIDs in the horse, the half-life of carprofen is long, with estimates ranging from 14 to 31 h (Lees et al 1994, McKellar et al 1991). Despite the slow clearance, there was no evidence of accumulation of carprofen in plasma when... 

DRUG INTERACTIONS As do other NSAIDs, the propionic acid derivatives may interfere with the action of antihypertensive and diuretic agents, increase the risk of bleeding with warfarin, and increase the risk of bone marrow suppression with methotrexate. Ibuprofen also has been... 

Naproxen, a propionic acid derivative, is a nonsteroidal antiinflammatory agent (NSAIA). The drug is structurally and pharmacologically related to fenoprofen and ibuprofen (1). 

Propionic acid derivatives Propionic acid derivatives, including ketoprofen and carpro-fen, can cause photosensitivity when used topically or systemically [9 ]. Occupational exposure can also result in photosensitivity. Consort contact dermatitis to such agents used topically is rare in the occupational setting, although it may occur when there is close physical contact with others [10 ]. 

The main group of methods for the preparation of a 1,2,4-oxadiazole ring is based on cyclization of amidoxime derivatives in the presence of acylating agents °. A surprisingly easy cyclization of O-benzoyl-/ -piperidinopropioamidoxime 247 to oxadiazole 248 in DMSO at room temperature was described (equation 107) . 3-(3-Aryl-1,2,4-oxadiazol-5-yl)propionic acids 250 were obtained by the reaction of amidoximes 249 with succinic anhydride under microwave irradiation or conventional heating (equation 108) °°. 

Beccalli et al. reported a new synthesis of staurosporinone (293) from 3-cyano-3-(lH-indol-3-yl)-2-oxo propionic acid ethyl ester (1464) (790). The reaction of 1464 with ethyl chlorocarbonate and triethylamine afforded the compound 1465, which, on treatment with dimethylamine, led to the corresponding hydroxy derivative 1466. The triflate 1467 was prepared from 1466 by reaction with trifluoromethanesulfonic anhydride (Tf20) in the presence of ethyldiisopropylamine. The palladium(O)-catalyzed cross-coupling of the triflate 1467 with the 3-(tributylstannyl)indole 1468 afforded the vinylindole 1469 in 89% yield. Deprotection of both nitrogen atoms with sodium ethoxide in ethanol to 1470, followed by photocyclization in the presence of iodine as the oxidizing agent provided the indolocarbazole 1471. Finally, reductive cyclization of 1471 with sodium borohydride-cobaltous chloride led to staurosporinone (293) in 40% yield (790) (Scheme 5.248). 

The alkylation products are synthetically useful because simple subsequent transformations furnishes precursors of important natural products as illustrated in Scheme 8E.23. Simple oxidative cleavage of allylic phthalimide 45 generates protected (5)-2-aminopimelic acid, whose dipeptide derivatives have shown antibiotic activity. The esterification via deracemization protocol is not limited to the use of bulky pivalic acid. The alkylation with sterically less hindered propionic acid also occurs with high enantioselectivity to give allylic ester 116, which has been utilized as an intermediate towards the antitumor agent phyllanthocin and the insect sex excitant periplanone. Dihydroxylation of the enantiopure allylic sulfone gives diol 117 with complete diastereoselectivity. Upon further transformation, the structurally versatile y-hydroxy-a,(f-un-saturated sulfone 118 is readily obtained enantiomerically pure. 

The chromatographic capacity factor (AT ) for ester and amide derivatives of 6,6a, 7,8,9,10,10a, 11-octahydro-ll-oxodibenzo[ /]thiepine propionic acid 44, potent antiinflammatory agents, has been studied, since the parameter was widely used for the interpretation of the activity of drugs <2003RRC795>. K, was modeled topologically using molecular redundancy index (MRI), equalized electronegativity (xeq), and van der Waals volume (fw)-... 

Propionic acid propanoic acid) derivatives have been extensively developed since the original introduction of ibuprofen into clinical use. Other examples of those in clinical use include fenbufen, flurbiprofen, ketoprofen, naproxen and oxaprozin. Many of these agents have a relatively low incidence of reported side-effects, however, their usage varies. Ibuprofen is the first analgesic since paracetamol to be licensed in the UK for non-prescription use but such use is limited to the treatment of relatively minor pain states, even though it has fair antiinflammatory properties. Most other members are reserved for systemic use to treat rheumatoid and osteoarthritis, musculoskeletal pain and similar states (some applied topically). 

Polyether lonophores. Isolation and identification of antibiotic X-14885A was reported.Its structure is closely related to A-23187 and cezomycin, members of the pyrrolether class of natural ionophores. Aspects of the discovery and ionophoric properties of the X-14868 complex were described. Another new naturally derived agent, CP-53607 (32), was reported to be effective t ainst coccidia and as a rumen propionic acid stimulant. The C-26 urethane analogs of monensin transported both Rb and Ca. Their antibacterial and anticoccidial activities were also reported as greater than monensin. Microbial conversion of grisorixin by Streptomyces rimosus was found to produce an inactive and detoxified product. A unified stereochemical model of polyether antibiotic structure and biogenesis was proposed. Ibtal synthesis of ionophores continued to be of interest and the unnatural enantiomer of lasalocid A was found to have similar biolc cal properties to the natural product. ... 

Derived agents such as benzoic acid, sodium benzoate, sorbic acid, and propionic acid, some of them having been used in edible coatings. Zeolites have also been incorporated in packages to release ions, or enzymes able to release antimicrobials as hydrogen peroxide. 

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