الفهرس 
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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.