Synthesis of some new 2,6-disubstituted-3(2 H )-pyridazinone derivatives and investigation of their analgesic, anti-infl
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Med Chem Res (2013) 22:2553–2560 DOI 10.1007/s00044-012-0253-1
ORIGINAL RESEARCH
Synthesis of some new 2,6-disubstituted-3(2H)-pyridazinone derivatives and investigation of their analgesic, anti-inflammatory and antimicrobial activities Didem Tiryaki • Murat Sukuroglu • Deniz S. Dogruer Esra Akkol • Selda Ozgen • M. Fethi Sahin
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Received: 29 June 2012 / Accepted: 20 September 2012 / Published online: 29 September 2012 Springer Science+Business Media New York 2012
Abstract In this study, 12 new 3(2H)-pyridazinone derivatives carrying 4-substituted phenylpiperazinylethyl moiety on lactam nitrogen were synthesized and their chemical structures were confirmed by 1H-NMR, mass, and elemental analysis. Analgesic and anti-inflammatory activities of the synthesized compounds were evaluated in mice. Among the synthesized compounds, compound 9c showed the best analgesic and anti-inflammatory activities without causing any gastric effect in stomachs of tested animals. In addition, the synthesized compounds were screened for their antibacterial and antifungal activities against some pathogenic strains. Keywords 3(2H)-pyridazinone Analgesic activity Anti-inflammatory activity Antimicrobial activity
Introduction Non-steroidal anti-inflammatory drugs (NSAIDs) are important therapeutic agents for the treatment of pain, fever, and inflammation associated with a number of pathological conditions. Especially, NSAIDs are the first choice in the
D. Tiryaki M. Sukuroglu D. S. Dogruer (&) M. F. Sahin Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330 Etiler, Ankara, Turkey e-mail: [email protected] E. Akkol Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Etiler, Ankara, Turkey S. Ozgen Department of Microbiology, Faculty of Pharmacy, Gazi University, 06330 Etiler, Ankara, Turkey
treatment of rheumatic disorders and other degenerative inflammatory joint diseases. The main mechanism of action of these drugs is the inhibition of cyclooxygenase enzyme (COX) which is catalyzing the conversion of arachidonic acid to the prostaglandins (PGs) mediating both inflammation response and physiologic homeostasis. Accordingly, chronic use of NSAIDs is often accompanied by side effects such as gastrointestinal lesions, bleeding, and nephrotoxicity (Williams and Lemke, 2008). In the early 1990s, two isoforms of the COX enzyme, known as COX-1 and COX-2, have been identified (Masferrer et al., 1992). Subsequent studies showed that COX-1 is a constitutive enzyme and synthesizes PGs mediating normal homeostasis in the gastrointestinal tract, kidneys, and platelets, whereas COX-2, mostly inducible, is related to the production of PGs mediating inflammation, pain, and fever (Dannhardt and Laufer, 2000). In the meantime, classical NSAIDs were determined to inhibit both isoforms (Dannhardt and Lauferm, 2000). These findings have led to the development of selective COX-2 inhibitors to improve the therapeutic potency and to reduce the classical side effects coupled with the us
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