4-[(5-DIFLUOROMETHYL-3-PHENYL)-4-ISOXAZOLYL]BENZENESULFONAMIDE

Chemical Properties

Celecoxib (Celebrex) and rofecoxib (Vioxx) are the two available COX-2 inhibitors. Both lack a carboxylic group present in most NSAIDs and therefore are able to orient into the COX-2 enzyme in a selective manner that differs from that of other NSAIDs.They have low aqueous solubility that prevents parenteral administration.

Uses

4-[5-(Difluoromethyl)-3-phenyl-4-isoxazolyl]benzenesulfonamide is a COX-??2 inhibitor which has been shown to modifiy voltage gated potassium 2.1 channel gating and, at high concentrations, induce some immunomodulatory effects.

Mechanism of action

As previously discussed, the COX-2 inhibitors have selectivity for inhibition of the COX-2 enzyme, which has low constitutive activity but is highly inducible at sites of tissue injury. In addition to the peripheral role of COX-2 in inflammation, COX-2 may play an important role in the CNS. COX-2 is expressed constitutively in some excitatory neurons in the brain and spinal cord and is induced in traumatic brain injury such as that induced by ischemia and seizures. It has been hypothesized that COX-2 may also be involved in neurodegenerative diseases, since COX-2 inhibitors have shown some positive effects in Alzheimer’s disease. Thus, the mechanism of action of COX-2 inhibitors may involve brain and spinal cord sites as well as local sites of injury.

Clinical Use

Celecoxib has been approved for the treatment of osteoarthritis and rheumatoid arthritis, and rofecoxib has been approved for the treatment of osteoarthritis, acute pain and primary dysmenorrhea. Celecoxib and rofecoxib do not appear to differ in efficacy for the treatment of osteoarthritis. However, neither drug has efficacy greater than that of the non-selective NSAIDs. Since the COX-2 enzyme appears to play an important role in colon cancer the COX-2 inhibitors may find future uses in the treatment or prevention of colorectal cancer.

Side effects

The major advantage of the COX-2 inhibitors is their decreased GI effects and formation of gastric ulcerations compared with the COX nonselective agents. However, once an ulcer is present, COX-2 is induced in response, and the COX-2 enzyme is essential for wound healing.Therefore, celecoxib and rofecoxib can delay in wound healing and increase the time for ulcer repair and tissue regeneration. Patients with gastric ulcers should be switched if possible to another antiinflammatory to allow ulcers to heal.
Celecoxib is contraindicated during pregnancy, since COX-2 levels must be maintained for ovulation and onset of labor. COX-2 seems to be involved into the regulation of the renin–angiotensin system, and both celecoxib and rofecoxib use are associated with transient sodium retention.

Raw materials

Preparation Products