Synthesis and Analgesic and Antiinflammatory Activity of Methyl 6‐Substituted‐3(2H)‐pyridazinone‐2‐ylacetate Derivatives

Abstract

A series of methyl 6-substituted-3(2H)-pyridazinone-2-ylacetates 9 were synthesized and their analgesic and anti-inflammatory effects were evaluated in the phenylbenzoquinone-induced writhing test (PBQ test) and carrageenan-induced paw edema method, respectively. Side effects of the compounds were examined on gastric mucosa. None of the compounds showed gastric ulcerogenic effect compared with reference nonsteroidal anti-inflammatory drugs. Methyl 6-(4-(4-fluorophenyl)piperazine)-3(2H)-pyridazinone-2-ylacetate 9e was found to be more active than acetylsalicylic acid (ASA). Methyl 6-(4-(2-ethoxyphenyl)piperazine)-3(2H)-pyridazinone-2-ylacetate 9c has shown an anti-inflammatory activity as compared to the standard compound indometacin at the carrageenan-induced paw edema method.A significant dependence of the anti-inflammatory effect on the substituents has been observed. The pharmacological study of these compounds confirms that modification of the chemical group at the position 6 of the 3(2H)-pyridazinone system influences analgesic and anti-inflammatory activities. The structures of these new pyridazinone derivatives were confirmed by their IR and (1)H-NMR spectra and elemental analysis.

Facile synthesis of multi‐functional 1,3,4‐thiadiazine derivatives bearing phthalazine, pyridazine, and pyrido‐pyridazine moieties

“…Nitrogen and sulfur heterocycles are omnipresent structural motifs found in numerous pharmaceuticals and bioactive natural products . Pyridazine derivatives have diverse biological activities including antihistaminic, analgesic, and anti‐inflammatory . The pyrido‐pyridazine ring is very attractive for many pharmaceutical industries because of the variety of their biological applications .…”

Synthesis, Computer Aided Screening and Pharmacological Evaluation of 2/3-Substituted-6(4-Methylphenyl)-4,5-Dihydropyridazin3(2h)-Ones, and Pyridazine Substituted Triazine

“…The currently used anti-inflammatory and analgesic compounds inhibit the synthesis of non selective or selective cyclooxygenases (COX1 & COX2) or prostaglandin, histamine and bradykinin (Sahina, et al, 2004;Dogruer, et al, 2003;Tazkoparan et al, 2000). It has been suggested that prostaglandins and bradykinins play a major role in the analgesia or pain.…”

Synthesis of Some Novel Heterocyclic Xylidinyl Amines and Carboxamides

“…This class of compounds is reported to show aldose‐reductase inhibitory effect . They are also used as antihistaminic, analgesic, anti‐inflammatory , and cardiotonic agents with vasodilator activity . In addition, these compounds were also reported to possess a good binding affinity toward α 1 ,α 2 ‐adrenergic and 5‐HT 1A serotoninergic receptors and to show herbicidal and fungicidal activities.…”