A Review on Pyridazinone Compounds ABT-963 as Selective Cyclooxygenase Inhibitor

Nonsteriodal anti-inflammatory drugs (NSAIDs) are efficacious for the treatment of pain associated with inflammatory disease. Selective cyclooxygenase-2 (COX-2) inhibitors (such as celecoxib, rofecoxib, and valdecoxib) have used in the treatment of inflammatory pain with an improved gastrointestinal tract (g.i.t) safety profile relative to conventional NSAIDs. These COX-2 inhibitors contain a core heterocyclic ring with two appropriately substituted phenyl rings appended to adjacent atoms.

The NSAIDs constitute an important class of drugs with therapeutic applications and used in the treatment of inflammatory conditions such as rheumatoid arthritis (RA) and osteoarthritis (OA) starting from the classic drug aspirin to the recent rise and fall of selective COX-2 inhibitors. The study their mechanism of action at the molecular level such as cyclooxygenase (COX) inhibition, development of selective COX-2 inhibitors, their adverse cardiovascular effects. The recent developments targeted to the design of effective antiinflammatory drugs with reduced side effects.

The structural basis for COX-1 and COX-2 inhibition is described along with methods used to evaluate COX-1/COX-2 inhibition. Some of the recent advances toward developing effective anti-inflammatory agents such as nitric oxide donor NO-NSAIDs, dual COX/LOX inhibitors and anti-TNF therapy. A great deal of progress has been made toward developing novel anti-inflammatory agents. The design and development of a safe, effective and economical therapy  for treating inflammatory conditions still presents a major challenge.

Prostaglandins (PG) play a significant role in the maintenance of homeostasis and in the body’s response to the environment. Two isozymes of cyclooxygenase (COX) are responsible for the biosynthesis of these mediators commonly called COX-1 and COX-2. Xie et al.and Smith have proposed that COX-2-generated PGs are mediators of inflammation, cellular proliferation, and pain, whereas COX-1-generated PG are involved in homeostasis in the stomach, kidney, and blood coagulation.

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