Overview on Emorfazone and Other Related 3(2H) Pyridazinone Analogues Displaying Analgesic and Anti-Inflammatory Activity

A series of structurally varied derivatives of 3(2H)-pyridazinone were tested for their analgesic and anti-inflammatory activity by using different test models. The analgesic and anti-inflammatory activity of the compounds were found to be significant as compare with reference drugs. Some of the 3(2H)-pyridazinone derivatives are having analgesic and anti-inflammatory activities. Pyridazine derivatives, Emorfazone is a non-steroidal analgesic anti-inflammatory drug which is clinically used for ailments such as pain, inflammation and rheumatoid arthritis. Various pyridazine derivatives also exhibited non-steroidal analgesic anti-inflammatory activity. INTRODUCTION The majority of currently known non-steroidal antiinflammatory and analgesic drugs (NSAIDs), i.e, aspirin and ibuprofen, mainly act peripherally by blocking the production of prostaglandins through inhibition of cyclooxygenase (COX) enzymes, COX-1 and COX-2, to varying extents [1]. These drugs tend to produce side effects such as gastrointestinal ulceration and suppression of renal function due to inhibition of the constitutive COX-1, which is responsible for the production of prostaglandins (PGs), responsible for gastro protection and vascular homeostasis [2-4]. Therefore, the main trend nowadays in pain therapy focuses on improved nonsteroidal analgesics which are effective as an analgesic but devoid of the side effects which are inherent to traditional NSAIDs. In terms of this aspect, many studies have been focussed on 3(2H)-pyridazinones, which are characterized to possess good analgesic and antiinflammatory activities and also very low ulcerogenicity [59]. Among the various pyridazinone derivatives, 4-ethoxy2-methyl-5-morpholino-3(2H)-pyridazinone (emorfazone) is being marketed in Japan as an analgesic and anti-inflammatory drug [10,11]. The 4-amino-2-methyl-6-phenyl-5-vinyl-3(2H)pyridazinone (Figure 1) was seven-fold more potent than emorfazone (Figure 1) [12-14] in bringing about analgesic and anti-inflammatory response. Additionally, 2-substituted 4, 5-dihalo-3(2H)-pyridazinone derivatives with high analgesic activity and with no ulcerogenic side effects [15]. Subsequently, 2-substituted 4,5-functionalized 6-phenyl-3(2H)-pyridazinone derivatives have also been reported to bear potent analgesic activity with negligible general side effects as those of currently used NSAIDs [16]. In the meantime, 3-O-substituted benzyl pyridazinone derivatives were shown to exhibit in vitro potent anti-inflammatory activity [14,17]. As a continuation of work for the development of improved NSAIDs; which are effective but devoid of the well-known side-effects linked with the obligatory use of NSAIDs, we also got interested in 3(2H)-pyridazinones [18-21] , which resulted in good analgesic and anti-inflammatory activities. Purpose: Non steroidal anti-inflammatory drugs (NSAIDs) constitute an important class of drugs with therapeutic applications. Treatment of inflammatory disorders likes rheumatoid arthritis (RA) and osteoarthritis (OA) starting from the classic drug to the recent rise and fall of selective COX2 inhibitors. Efforts to discover drug to treat inflammation