Arthritis, treatment cyclooxygenase-2 inhibitors

The so-called COX (cyclooxygenase) inhibitors are widely applied in the treatment of acute and chronic pain and inflammation, that is, in rheumatoid arthritis and osteoarthritis. The characterization of the correlation between the plasma concentration of COX inhibitors and their pain- and inflammation-decreasing ability is often done via inflammation biomarkers such as PGE2 and thromboxane B2. 

The major problem of NSAIDs is gastrointestinal (GI) irritation, leading to ulceration. Recent drugs such as celecoxib (a cyclooxygenase-II inhibitor) have a mild effect on the GI tract and have proven to be the drugs of choice for the treatment of rheumatoid arthritis. 

Pfizer) are selective cyclooxygenase type 2 (COX-2) inhibitors and are useful in the treatment of arthritis. The compounds exert their pharmacological effect by selectively blocking the COX-2 enzyme to produce an antiinflammatory effect without adverse gastrointestinal side effects. In addition, they also display analgesic and antipyretic activities in animal models. 

Celecoxib is a selective COX-2 inhibitor/GI agent that reduces inflammation (e.g., pain, redness, swelling, heat), fever, and pain by inhibiting chemicals in the body that cause inflammation, fever, and pain. This is probably caused by the inhibition of prostaglandin synthesis, primarily via inhibition of cyclooxygenase-2 (COX-2) isoenzyme. Celecoxib is indicated in relief of symptoms of osteoarthritis relief of symptoms of rheumatoid arthritis in adults management of acute pain in adults treatment of primary dysmenorrhea and reduction of the number of adenomatous colorectal polyps in familial adenomatous polyposis (FAP), as an adjunct to usual care (e.g., endoscopic surveillance, surgery). 

A noted example is found in the development of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib (132) for the treatment of rheumatoid arthritis. Synthetic routes to celecoxib demonstrate two important strategies for constructing the trifluoromethyl pyrazole moiety. In the initial synthesis, a key step was the reaction of an aryUiydrazine with the enol ether 133 prepared by condensation of ethyltrifluoroacetate with the substituted acetophenone. Two regioisomers are formed, but the desired 1,5-pyrazole predominates when the condensation is performed with the arylhydrazine hydrochloride in refluxing ethanol (Fig. 3.78). ... 

Etoricoxib is a selective cyclooxygenase (COX-2) inhibitor, approved in Europe for the symptomatic treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and acute gouty arthritis. Etoricoxib does not have Food and Drug Administration approval. 

---