Investigations of New Pyridazinone Derivatives for the Synthesis of Potent Analgesic and Anti‐Inflammatory Compounds with Cyclooxygenase Inhibitory Activity

Abstract

In this study we describe the synthesis of two novel 4-phenyl-and 4-(2-chlorophenyl)-6-(5-chloro-2-oxo-3H-benzoxazol-7-yl)-3(2H)-pyridazinone derivatives (compounds 8a and b) and their testing as inhibitors of cyclooxygenases (COX-1 and COX-2). Both compounds inhibited COX-1 (by 59 % and 61 % for compounds 8a and 8b respectively and COX-2 (by 37 % and 28 % for compounds 8a and 8b respectively) at a concentration of 10 microM. Furthermore, we tested the analgesic and anti-inflammatory activities of the synthesized compounds in vivo by using the p-benzoquinone-induced writhing test and the carrageenan-induced hind paw edema model, respectively. Compounds 8a and 8b showed potent analgesic and anti-inflammatory activities without causing gastric lesions in the tested animals.

An Efficient Synthesis and Reactions of Novel Indol-ylpyridazinone Derivatives with Expected Biological Activity

“…In recent years a substantial number of 6-aryl-3-(2H)-pyridazinones have been reported to possess antimicrobial [1,2], potent analgesic [3], anti-inflammatory [3][4][5][6][7], antifeedant [8], herbicidal [9], antihypertensive [10][11][12] and antiplatelet activities [13][14][15], anticancer effects [16] and other anticipated biological [17] and pharmacological properties [18,19]. In particular, a large number of indolylpyridazinone derivatives are well known as antimicrobial agents [1,20], intermediates for drugs and agrochemicals [21,22], antiphlogistics [23], antipyretics [24], inflammation inhibitors [25], blood platelet aggregation inhibitors, cardiovascular and antihypertensive agents [26].…”

Synthesis and Antimicrobial Activities of Some New Thieno and Furopyrimidine Derivatives

“…After completing the reaction, the mixture was cooled to room temperature and ethanol was added whereby a yellow precipitate was obtained. [1,2,4]triazolo [4,3-c]thieno [3,2-e]pyrimidine (6):…”

“…Further more, many condensed heterocyclic systems, especially when linked to a pyrimidine ring as thienopyrimidine play an important role as potent analgesic [1], anti-inflammatory [1][2][3][4][5], antipyretic [6][7][8], antimicrobial [9][10], anticonvulsant [11], fungicidal [12], antiplatelet activities [13][14][15], and other central nervous system (CNS) affecting activities [16]. In addition, pyrimidine nucleus can be found in a broad variety of antibacterial, anticancer and anti-tumor agents as well as in agrochemicals and veterinary products [17][18].…”

Convenient synthesis of some methyl-N-[2-(3-oxo-6-p-tolyl-2,3,4,5-tetrahydropyridazin-2-yl)-acetylamino]amino acid esters

“…Recently, a number of 6-aryl-4,5-dihydropyridazin-3(2H)-ones have been reported to possess antimicrobial, 1,2 potent analgesic, 3 anti-inflammatory, [3][4][5][6][7] antifeedant, 8 herbicidal, 9 antihypertensive, [10][11][12] antiplatelet activities, [13][14][15] anticancer effects 16 and other anticipated biological 17 and pharmacological properties. 8,19 Imazodan I is reported to show ionotropic properties comparable to milrinone and amrinone II.…”