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Abstract Title: Design and Synthesis Derivatives of Para- MethylSulfonylAcetophenone as Potential Anti- Inflammatory Agents. Keywords: NSAIDS- COX1- COX 2- Coxibs- phenyl thiazole, oxazole derivatives, anti- inflammatory agents, ulcerogenic liability. In this research, some novel para-methylsulfonyl oxazole, thiazole and thiazole-4-one were synthesized. The newly synthesized compounds were evaluated for their in-vivo anti- inflammatory activity and in-vitro selective COX-2 inhibition. Also, analgesic and ulcerogenic liability for the most active compounds were done. The most potent compounds were docked inside the active site of COX-2 enzyme to predict their mechanism of action. The thesis includes the following parts: 1. Introduction: This part includes a brief literature review on inflammation, various reported anti- inflammatory compounds having substituted phenyl oxazole and thiazole derivatives with COX-2 selectivity, ulcerogenic liability and analgesic activity of the most active compounds were done. 2. Research Objectives: This part includes the schemes, pathways and scientific bases for synthesizing novel phenyl thiazole , oxazole and thiazolidinone. 3. Discussion: This part deals with the discussion of experimental methods and conditions of reactions adopted for the synthesis of the prepared compounds 4. Experimental: This part includes the practical procedures for the synthesis of new compounds and their elemental analyses and spectral data (IR, 1H-NMR and mass spectroscopy). VIII This thesis comprises the synthesis of the following unavailable reported starting materials and intermediates: 1) 2-Bromo-1-(4-(methyl sulfonyl) phenyl ) ethanone II In addition, the study comprises the synthesis of the following new targeted compounds: 2) 2-(Dimethylamino)-1-(4-(methylsulfonyl) phenyl) ethanone IIIa 3) 2-(Diethylamino)-1-(4-(methylsulfonyl) phenyl) ethanone IIIb 4) 1-(4-(Methylsulfonyl) phenyl)-2-(pyrrolidin-1-yl) ethanone IIIc 5) 2-(4-Chlorophenylamino)-1-(4-(methylsulfonyl) phenyl) ethanone IIId 6) 2-(4-Nitrophenylamino)-1-(4-(methylsulfonyl) phenyl) ethanone IIIe 7) 2-(4-Methoxyphenylamino)-1-(4-(methylsulfonyl) phenyl) ethanone IIIf 8) 2-Methyl-4-(4-(methylsulfonyl) phenyl) oxazole IVa 9) 2-(4-Chlorophenyl)-4-(4-(methylsulfonyl) phenyl) oxazole IVb 10) 4-(4-(4-(Methylsulfonyl) phenyl) oxazol-2-yl) benzenamine IVc 11) 2-Chloro-N-(4-(4-(methylsulfonyl) phenyl) thiazol-2-yl)acetamide VI 12) N-(4-(4-(Methylsulfonyl) phenyl) thiazol-2-yl)-2-(pyrrolidin-1-yl) acetamide VIIa 13) N-(4-(4-(Methylsulfonyl) phenyl) thiazol-2-yl)-2-morpholino acetamide VIIb 14) N-(4-(4-(Methylsulfonyl) phenyl) thiazol-2-yl)-2-(piperidin-1-yl) acetamide VIIc 15) 2-(4-Methylpiperazin-1-yl)-N-(4-(4-(methylsulfonyl) phenyl) thiazol-2-yl) acetamide VIId 16) 2-(4-Chlorophenylamino)-N-(4-(4-(methylsulfonyl) phenyl) thiazol-2-yl)acetamide VIIe 17) 2-(4-Nitrophenylamino)-N-(4-(4-(methylsulfonyl) phenyl) thiazol-2-yl) acetamide VIIf 18) 2-(4-Methoxyphenylamino)-N-(4-(4-(methylsulfonyl) phenyl) thiazol-2-yl)acetamide VIIg 19) 2-(4-(4-(Methylsulfonyl) phenyl) thiazol-2-ylamino) thiazol-4(5H)-one IX 20) 2-(4-(4-(Methylsulfonyl) phenyl) thiazol-2-ylamino)-5-benzylidenethiazol-4(5H)-one IXa 21) 2-(4-(4-(Methylsulfonyl) phenyl) thiazol-2-ylamino)-5-(4-chlorobenzylidene) thiazol-4(5H)- one IXb 22) 2-(4-(4-(Methylsulfonyl) phenyl) thiazol-2-ylamino)-5-(4-nitrobenzylidene) thiazol-4(5H)- one IXc IX 23) 2-(4-(4-(Methylsulfonyl) phenyl) thiazol-2-ylamino)-5-(4-methoxybenzylidene) thiazol- 4(5H)-one IXd 5. Pharmacological activity: New synthesizing compounds were screened for their In-vitro, in-vivo anti- inflammatory activity using formalin edema method. Moreover, the most active compounds were screened for analgesic activity and ulcerogenic liability. 6. Molecular modeling: The most active compounds were docked in the active site of COX-2 to predict the expected mechanism of action. 7. Conclusion: It clarifies the correlation between the results of molecular docking and the anti- inflammatory activity. 8. References: This part includes 110 references 9. Arabic summary. |