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Abstract This thesis comprises four chapters. The first one is an introduction that comprises a hint on biological view of inflammation and different drugs used in its treatment. It also includes the different methods adopted to synthesize some diaryl and triarylheterocycles with apyrazole, pyrazolineor pyridine ascentral ring. The second chapter deals with the aim of this work and schemes thosehad been carried out to obtain the target compounds. The third chapter clarifies the discussion of the experimental work for the preparation of starting materials Ia&b, IIa&b, III,IVa&b, Va-dand Xc-min addition to twoknown compounds IXbandXIIIc. Compounds VIa-dand VIIa-dwere synthesized by cyclization of certain chalconesVa-dwith malononitrile in presence of either ammonium acetate or sodium methoxidein sequent. In addition, compounds VIIIa-dwere synthesized by cyclization of a series of chalconesVa-dwith ethyl cyanoacetate in presence of ammonium acetate. Also, the reaction of chalconesVa,c,dwith hydrazine hydrate in presence of glacial acetic acid as solvent affordedthe pyrazolodervativesIXa,c,d. Furthermore, cyclization of chalconesXa-mwithp-sulfamylphenylhydrazine hydrochloride(Ia) afforded 1,3,5-triaryl-2-pyrazolines XIa-mthrough Michael addition reaction. On the other hand, cyclization of chalconesVb&dwith Ia afforded the intermediate hydrazoneXIIa&b. Moreover, the condensation of β-diketoneIIa,b,III and IVa,bwith either Iaor Ib afforded 1,5-diaryl-pyrazole derivatives XIIIa,b,XIIIdand XIIIe-jrespectively. Finally, the acid derivativesXIVa-dwere synthesized by hydrolysis of the corresponding esters XIIIe-j. The fourth chapter consists of the experimental part of this work which contains the detailed procedures used for the synthesis of the starting materials Ia&b, IIa&b, III, IVa&b, Va-d, Xa-min addition to the final compoundsVIa-d,VIIa-d, VIIIa-d, IXa-d, XIa-m, XIIa&b, XIIIa-jand XIVa-d. In addition, the data obtained from the elemental and spectral analysis as well as their physical properties is given in this chapter. It also sheds the light on both in vivo and in vitro anti-inflammatory activity of thirty seven synthesized compounds compared with celecoxib, ibuprofen, etoricoxib and aspirin as standard anti-inflammatoryagents. In addition this chapter clarifies the ulcerogenic liabilityof thirty twosynthesized compoundscompared with celecoxib and ibuprofen as reference drugs. |