الفهرس 
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Abstract
In a search for new cytotoxic agents with improved antitumor activity and selectivity, some new thiazole, thiazolopyrimidine, thiazolopyrane and thiazolopyranopyrimidine derivatives bearing sulfonamide moiety were synthesized. The newly synthesized compounds were evaluated for their antitumor activity alone and in combination with γ-irradiation. These new compounds were docked inside the active site of carbonic anhydrase II to predict their mechanism of action.
The thesis includes the following parts: This part includes a brief literature review on cancer, chemotherapy and radiotherapy, rationale of combining chemotherapy and radiotherapy, the expected anticancer activity of new thiazole, thiazolopyrimidine and tricyclic pyrimidine derivatives, and different methods for the synthesis of these new compounds.
This part includes the biological bases on which the synthesized compounds were designed. Schemes illustrate the synthetic pathways adopted in the preparation of the target compounds. This part deals with the discussion of experimental methods adopted for the synthesis of the target compounds.
This part includes the detailed practical methods for the synthesis of twenty seven new compounds and five known intermediates that are listed below with their elemental analyses and spectral data (IR, 1H-NMR and mass spectroscopy).
Known intermediates:
• 2-Chloro-N-(4-sulfamoylphenyl) acetamide (II)
• 4-(4-Oxo-4,5-dihydrothiazol-2-ylamino)benzenesulfonamide (III)
• 4-Isothiocyanato benzenesulfonamide (V)
• 4-(4-Methylbenzylideneamino)benzenesulfonamide ( VIIIa)
• 4-(4-Nitrobenzylideneamino) benzenesulfonamide (VIIIb).
New compounds:
• 4-(7-Phenyl-5-thioxo-4,5,6,7-tetrahydrothiazolo[4,5-d]pyrimidin-2-ylamino) benzenesulfonamide (IVa)
• 4-(5-Thioxo-7-p-tolyl-4,5,6,7-tetrahydrothiazolo[4,5-d]pyrimidin-2-ylamino) benzenesulfonamide (IVb)
• Ethyl 2-cyano-3-(4-sulfamoylphenylamino)-3-thioxopropanoate (VI)
• Ethyl 2-(4-oxo-4,5-dihydrothiazol-2-yl)-3-(4-sulfamoylphenyl amino)-3-thioxopropanoate (VII)
• 4-(4-Oxo-2-p-tolylthiazolidin-3-yl) benzenesulfonamide (IXa)
• 4-(2-(4-Nitrophenyl)-4-oxothiazolidin-3-yl) benzenesulfonamide (IXb)
• 4-(4-Oxo-2-phenylthiazolidin-3-yl) benzenesulfonamide (IXc)
• 4-(2-(2-Hydroxyphenyl)-4-oxothiazolidin-3-yl) benzenesulfonamide (IXd)
• 4-(2-(4-Hydroxyphenyl)-4-oxothiazolidin-3-yl) benzenesulfonamide (IXe)
• 4-(2-(Benzo[d][1,3]dioxol-5-yl)-4-oxothiazolidin-3-yl) benzenesulfonamide (IXf)
• 4-(2-(2-Chlorophenyl)-4-oxothiazolidin-3-yl) benzenesulfonamide (IXg)
• 4-(2-(3-Bromophenyl)-4-oxothiazolidin-3-yl) benzenesulfonamide (IXh)
• 4-(5-Amino-6-cyano-7-(4-nitrophenyl)-7H-thiazolo[4,5-b]pyran-2-ylamino) benzenesulfonamide (XIa)
• 4-(5-Amino-6-cyano-7-(3,4-dimethoxyphenyl)-7H- thiazolo[4,5-b]pyran -2- ylamino) benzenesulfonamide (XIb)
• 4-(5-Amino-7-(2-chlorophenyl)-6-cyano-7H- thiazolo[4,5-b]pyran-2-ylamino) benzenesulfonamide(XIc)
• 4-(5-Amino-7-(3-bromophenyl)-6-cyano-7H- thiazolo[4,5-b]pyran-2-ylamino) benzenesulfonamide (XId)
• 8-Amino,9-(4-nitrophenyl) 9-H,[2-(4-sulfamoyl phenyl amino)] thiazolo[4,5-b]pyrano [2,3-d] pyrimidine (XII)
• 8-Oxo, 9-(4-nitro phenyl) 9-H,[2-(4-sulfamoyl phenyl amino)] thiazolo[4,5-b]pyrano [2,3-d] pyrimidine (XIIIa)
• 8-Oxo,9-(3,4-dimethoxy phenyl) 9-H,[2-(4-sulfamoyl phenyl amino)] thiazolo[4,5-b] pyrano [2,3-d] pyrimidine (XIIIb)
• 6-Methyl,8- oxo,9-(4-nitro phenyl) 9-H,[2-(4-sulfamoyl phenyl amino)] thiazolo[4,5-b] pyrano [2,3-d] pyrimidine (XIVa)
• 6-Methyl,8- oxo,9-(3,4-dimethoxy phenyl) 9-H,[2-(4-sulfamoyl phenyl amino)] thiazolo[4,5-b] pyrano [2,3-d] pyrimidine (XIVb)
• 8-Amino, 6-oxo ,9-(4-nitro phenyl) 9-H,[2-(4-sulfamoyl phenyl amino)] thiazolo[4,5-b]pyrano [2,3-d] pyrimidine (XV)
• 8-Amino, 6-thioxo ,9-(4-nitro phenyl) 9-H,[2-(4-sulfamoyl phenyl amino)] thiazolo[4,5-b] pyrano [2,3-d] pyrimidine (XVI)
• 4-(6-Cyano-7-(4-nitrophenyl)-2-(4-sulfamoylphenylamino)-7H- thiazolo[4,5-b]pyran-5-ylamino)-4-oxobutanoic acid (XVII)
• 4-(6-Cyano-5-(2,5-dioxopyrrolidinyl)-7-(4-nitrophenyl)-7H- thiazolo[4,5-b]pyran-2-ylamino) benzenesulfonamide (XVIII)
• N-(6-cyano-7-(4-nitrophenyl)-2-(4-sulfamoylphenylamino)-7H-pyrano[2,3-d]thiazol-5-yl)-3-oxobutanamide (XIX)
• 8-Imino, 6-thioxo, 9-(3,4-dimethoxy phenyl) 9-H,1N phenyl,[2-(4-sulfamoyl phenyl amino)] thiazolo[4,5-b]pyrano [2,3-d] pyrimidine (XX)
Twenty seven new compounds were screened for their in-vitro anticancer activity against human carcinoma liver cell line (HEPG2) while seven promising compounds were screened for their anticancer activity in combination with gamma irradiation to study the synergestic effect of combining chemotherapy and radiotherapy. All the newly synthesized compounds are docked in the active site of carbonic anhydrase II to predict the expected mechanism of action.
This part includes 127 references.