Acta Poloniae Pharmaceutica ñ Drug Research, Vol. 69 No. 3 pp. 411ñ421, 2012 ISSN 0001-6837 Polish Pharmaceutical Society Prostaglandins are endogenous substances involved in different processes of physiological nature and are potent mediators of inflammation. Prostaglandins are produced, together with other prostanoids, in the arachidonic acid metabolism, whose first step, consisting of the oxidative conver- sion of arachidonic acid into prostaglandin H 2 , is catalyzed by cyclooxygenase (COX) (1). This enzyme exists at least as two isoforms, one constitu- tive (COX-1) and the other inducible (COX-2) (2). COX-1 is found in platelets, kidneys, and in the gas- trointestinal (GI) tract, and is believed to be respon- sible for the homeostatic maintenance of the kidneys and GI tract. The COX-2 enzyme is the inducible isoform that is produced by various cell types upon exposure to cytokines, mitogens and endotoxins released during injury (3). The COX-2 enzyme, after being overexpressed at the site of injury, is a catalyst for the production of the prostaglandins that results in inflammation and pain at the site. COX-1 is involved in the maintenance of the GI tract; so all nonsteroidal anti-inflammatory drugs (NSAIDs) that are inhibitors of both COX-2 and COX-1 have been found to cause side effects associated with gas- trointestinal ulcers (4ñ6). Thus, it was thought that a more selective COX-2 inhibitor would have reduced gastrointestinal side effects (3). Several COX-2 selective inhibitors, including celecoxib (Celebrex) (7), valdecoxib (Bextra) (8), rofecoxib (Vioxx) (9), and etoricoxib (Arroxin) (10) have shown excellent efficacy in humans with few side effects. There is still a need to synthesize novel, potent anal- gesic/anti-inflammatory compounds that have reduced side effects when compared with the drugs currently available on the market. In recent decades, the literature has been enriched with progressive findings about the synthesis and pharmacological activities of pyrazole ring, which is a core structure DRUG SYNTHESIS SYNTHESIS AND ANTI-INFLAMMATORY EVALUATION OF NEW SUBSTITUTED 1-(3-CHLOROPHENYL)-3-(4-METHOXYPHENYL)- 1H-PYRAZOLE DERIVATIVES HODA H. FAHMY 1 , NAGY M. KHALIFA 1 *, EMAN S.NOSSIER 1 , MOHAMED M. ABDALLA 2 , and MAGDA M. F. ISMAI 3 1 Department of Therapeutical Chemistry, National Research Centre, El-Behoos Street, Dokki, 12622, Cairo, Egypt 2 Hi-Care Pharmaceuticals, Quesna, Monofya, Egypt 3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt Abstract: A series of heterocyclic derivatives including 1,2,4-triazole-3(4H)-one (3a,b), 1H-pyrazol-5(4H)-one (4,5), 1H-pyrazol-4-carbonitrile (7), pyridine-3-carbonitrile (8, 9a,b), pyrimidine-5-carbonitrile (10a,b), methylpyrimidin-2(1H)-one or thione (11a,b), pyrimidine-5-carboxylate (12a,b), quinazolin-5(6H)-one (13a,b) and indeno [1,2-d] pyrimidin-5-one (14a,b) moieties conjugated with 1,3-disubstituted pyrazole moiety were synthesized on reaction with semicarbazide, thiosemicarbazide, 3-amino-5-oxo-2-pyrazoline, cyanoacetohy- drazide, 2-acetyl thiophene, p-chloroacetophenone, urea, thiourea and 1,3-dicarbonyl compounds, respectively, by using 1-(3-chlorophenyl)-3-(4-methoxyphenyl)-1H-pyrazole-4-carboxaldehyde (2) as starting material. The structures of all the newly synthesized products have been established on the basis of analytical and spectral data. The anti-inflammatory screening showed that most of the obtained compounds were found to have sig- nificant anti-inflammatory activities with prostaglandin inhibition at a dose level of 2.5 and 5 mg/kg compara- ble to celecoxib as a reference control. The ulcer indices of all compounds are mainly in the safe level (UI = 2.10ñ4.27) except for compounds 9a and 14a, which were highly ulcerogenic. Keywords: pyrazole derivatives, anti-inflammatory, selective COX-2 inhibitor 411 * Corresponding author: e-mail: nagy.khalifa@hotmail.com