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      Analgesic and anti-inflammatory activities of several 4-substituted-6-(3'-nitrophenyl)pyridazin-(2H)-3-one derivatives

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          Abstract

          Several 6-aryl-4-substituted benzylidene/furfurylidene pyridazin(2H)-3-one derivatives (4a-f) were synthesized and evaluated as analgesic and anti-inflammatory agents in mice and rats, respectively. All compounds were tested by using Eddy's hot plate and the carrageenan-induced hind paw oedema method for the evaluation of analgesic and anti-inflammatory activities, respectively. Results showed that compounds 4f, 4b, 4d, and 4e exhibited higher analgesic and anti-inflammatory activities than other remaining compounds. All title compounds (4a-f) were characterized by IR, NMR and Mass spectroscopy.

          Translated abstract

          Diversos derivados benzilideno/furfurilideno piridazin(2H)-3-ona 6-aril-4-substituídos (4a-f) foram sintetizados e avaliados como analgésicos e anti-inflamatórios em camundongos e ratos, respectivamente. Todos os compostos foram testados utilizando-se o método de placa quente de Eddy e o de edema de pata induzido por carragenana para a avaliação das atividades analgésica e anti-inflamatória, respectivamente. Os resultados mostraram que os compostos 4f, 4b, 4d e 4e exibiram atividade analgésica e anti-inflamatória mais alta do que os compostos restantes. Todos os compostos (4a-f) foram caracterizados por IV, RMN e espectrometria de massas.

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          Most cited references28

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          New insights into the mode of action of anti-inflammatory drugs.

          The discovery of a second cyclooxygenase has provided fresh impetus to the search for new anti-inflammatory drugs. The second enzyme is effectively absent from healthy tissues but its levels rise dramatically during inflammation. It can be induced in migratory cells by bacterial lipopolysaccharide, cytokines and growth factors. The constitutive cyclooxygenase-1 (COX-1) can thus be considered a "housekeeping" enzyme, in contrast to cyclooxygenase-2 (COX-2) which is activated by tissue damage. Both enzymes have a molecular weight of around 70 kDa and similar Km and Vmax values for their reaction with arachidonic acid. Several non steroid anti-inflammatory drugs which have more than 1,000 fold selectivity for COX-2 over COX-1 are in the early stages of drug development.
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            Handbook of experimental Pharmacology

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              Gastrointestinal effects of nonsteroidal anti-inflammatory therapy.

              Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for the treatment of many conditions including rheumatoid arthritis, osteoarthritis, gouty arthritis, the joint and muscle discomfort associated with systemic lupus erythematosus, and other musculoskeletal disorders. Yet, their benefits, which are believed to be a result of their ability to inhibit cyclooxygenase-2 (COX-2), are accompanied by considerable toxicity. NSAIDs' untoward effects are attributed to their inhibition of the constitutively expressed enzyme cyclooxygenase-1 (COX-1), with attendant suppression of the synthesis of prostanoids, substances that mediate key homeostatic functions. Side effects include suppression of hemostasis through inhibition of platelet aggregation, adverse effects in patients with heart failure and cirrhosis, and those with certain renal diseases, as well as complicating antihypertensive therapies involving diuretics or beta-adrenoceptor blockade. Perhaps most importantly, NSAIDs disrupt the gastrointestinal mucosal-protective and acid-limiting properties of prostaglandins, frequently leading to upper gastrointestinal erosions and ulceration, with possible subsequent hemorrhage and perforation. These complications can be reduced through identification of patients at risk, with circumspect use of NSAIDs, careful functional monitoring, and, in the case of gastrointestinal toxicity, co-administration of such agents as misoprostol or omeprazole. However, these strategies introduce complexity into the treatment paradigm. Moreover, side effects and adverse events may be significantly reduced through the use of COX-2-specific inhibitors, new agents that alleviate pain and inflammation without the liability for adverse events caused by COX-1 inhibition.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                bjps
                Brazilian Journal of Pharmaceutical Sciences
                Braz. J. Pharm. Sci.
                Universidade de São Paulo, Faculdade de Ciências Farmacêuticas (São Paulo )
                2175-9790
                December 2013
                : 49
                : 4
                : 903-909
                Affiliations
                [1 ] Institute of Management and Technology India
                [2 ] Kumaun University India
                Article
                S1984-82502013000400030
                10.1590/S1984-82502013000400030
                b2419be7-9f0d-4b31-9e93-bc2704569bdd

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=1984-8250&lng=en
                Categories
                PHARMACOLOGY & PHARMACY

                Pharmacology & Pharmaceutical medicine
                Pyridazinone,Analgesics,Anti-inflammatories,Synthetic compounds,Piridazinona,Analgésicos,Anti-inflamatórios,Compostos sintéticos

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