Tenoxicam

Replacement of a benzene ring by its isostere, thiophene, is one of the more venerable practices in medicinal chemistry. Application of this stratagem to the NSAID piroxicam, gives tenoxicam, 136, a drug with substantially the same activity, nie synthesis of this compound starts by a multi-step conversion of hydroxy thiophene carboxylic ester 130, to the sulfonyl chloride 133. Reaction of that with N-methylglycinc ethyl ester, gives the sulfonamide 134. Base-catalyzed Claisen type condensation serves to cyclize that intermediate to the p-keto ester 135 (shown as the enol tautomer). The final product tenoxicam (136) is obtained by heating the ester with 2-aminopyridine [22]. 

Oxicams, e.g. piroxicam, tenoxicam, meloxicam and lornoxicam are non-specific inhibitors of COX. Like diclofenac, meloxicam inhibits COX-2 ten times more potently than COX-1. This property can be exploited clinically with doses up to 7.5 mg per day, but at higher doses COX-1-inhibition becomes clinically relevant. Since the dose of meloxicam commonly used is 15 mg daily, this agent cannot be regarded as a COX-2-selective NS AID and considerable caution needs to be exercised when making comparisons between the actions of meloxicam and those of other conventional NSAIDs. The average daily dose in anti-rheumatic therapy is 20 mg for piroxicam and tenoxicam, 7.5-15 mg for meloxicam and 12-16 mg for lornoxicam. Oxicams have long elimination half-lives (lornoxicam 3-5 h, meloxicam - 20 h, piroxicam 40 h and tenoxicam 70 h). 

CjHfiNj 504-29-0) see Fenyramidol Lornoxicam Mepyramine Piroxicam Propiram Risperidone Tenoxicam Zolimidine... 

C7H,j05S 97-05-2) see Domiodol 3-sulfo-2-thiophenecarboxylic acid (C5H4O5S2 59337-95-0) see Tenoxicam sulfuric acid zinc salt (1 1) heptahydrate (H 405SZn 7446-20-0) see Pyrithione zinc... 

Acenocoumarol, amiodarone, celecoxib, coumadin, dexamethasone, diclofenac, etoposide, fluconazole, fluoxetine, fluvas-tatin, fluvoxamine, ghmepiride, ghpizide, glyburide, ibuprofen, irbesartan, isoniazid, losartan, midazolam, phenylbutazone, phenytoin, rifampin, teniposide, tenoxicam, thiotepa, tolbutamide, torsemide, vitamin D, warfarin... 

Bioactive compounds from Blumea gariepina salicin, salicylic acid, tenoxicam, ketorolac, piroxicam, tolmetin, naproxen, flurbiprofin, diclofenac, and ibuprofen in pharmaceutical formulations and biological samples ... 

Apart from the salicylates NSAIDs include several classes of weak acids like propionic acid derivatives such as ibuprofen, carprofen, fenbufen, fenoprofen, flurbiprofen, ketorolac, loxoprofen, naproxen, oxaprozin, tiaprofenic acid and suprofen. Phenylbutazone is the most important representative of the pyrazolon derivatives which have a bad reputation for their risk of potentially fatal bone-marrow toxicity. To the acetic acid derivatives belong in-domethacin, diclofenac and sulindac. Sulindac is a pro-drug with less toxicity than indomethacin. The enolic acids include piroxicam, droxicam and tenoxicam. Meloxicam is an analog of piroxicam and has a high selectivity for COX-2. 

The most biologically active members of the benzothiazines, known as the oxicams, include piroxicam (Feldene ) 21, meloxicam (Mobic ) 22, and tenoxicam 23 which have a 1,2-benzothiazine 1,1,4-trioxide structure. Recently, the... 

Tenoxicam is a congener of piroxicam with similar properties and uses. 

Benzene and thiophene rings can of course often be interchanged in biologically active agents. The very broad structural latitude consistent with NSAID activity is by now a familiar theme as well. Preparation of the fused thiophene counterpart of the NSAID piroxicam (Chapter 11) starts with the reaction of thiophene (25-1), itself the product of a multistep sequence, with ethyl A-methylglycinate to give the sulfonamide (25-2). Treatment of that intermediate with a base leads to intramolecular Claisen condensation and thus the formation of the 3-ketoester (25-3). An amide-ester interchange with 2-aminopyridme (25-4) completes the synthesis of tenoxicam (25-5) [25]. 

Azapropazone, carprofen, meclofenamate, and tenoxicam are rarely used and are not reviewed here. 

Clinical use Tenoxicam (Todd and Clissold, 1991) is a nonsteroidal anti-inflammatory drug used for the treatment of mild to moderate pain states in musculoskeletal, soft tissue and joint disorders such as rheumatoid arthritis, osteoarthritis and gout. 

Tenoxicam is given by oral, rectal or intramuscular routes (20 mg/day, maximal dose 40 mg/day). 

Peak plasma concentration appears within 1 to 6 h depending on fasted or fed status. There is 99% binding of tenoxicam to plasma proteins and a long plasma elimination half-life of 49 to 81 h. Tenoxicam is eliminated by liver metabolism. The main metabolites are 5 -hydroxy-tenoxicam and the 6-O-glucuronidate which are excreted in urine and bile, respectively (Nilsen, 1994). The hydroxylated metabolites of tenoxicam are shown in Scheme 84 ... 

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