Shaker Youssif

Synthesis and Some Pharmacological Studies of New Benzenesulfonamide Derivatives

Summary. New benzenesulfonamide derivatives containing pyrazole and oxadiazole moieties were prepared starting from sodium saccharin. The structures of the novel compounds were characterized by elemental analyses and spectroscopic methods. The new compounds are structurally related to the COX-2 inhibitor celecoxib (Celebrex®). A pharmacological study of the pyrazoles revealed that several compounds possess higher analgesic and antiinflammatory activities than celecoxib, particularly 11 and 17. Most of the pyrazoles showed a significant increase in the sleeping time of thiopentone anaesthesized mice and also protected mice against the convulsive and lethal effects of pentylenetetrazole. Moreover, the ulcerogenic activity of those compounds showing a pronounced antiinflammatory effect was also studied.

6-Aminouracils as precursors for the syntheses of fused di- and tricyclic pyrimidines

The treatment of 1-benzyl-, or 1-methyl-6-chlorouracil (1a,b) with nucleophilic primary amines followed by nitrosation, reduction, formylation and dehydro-cyclisation lead to xanthines 5 and 7. While, the treatment of uracil 8 with aromatic aldehydes 9a–f leads to the formation of dipyrimidinopyridines 10a–f, reaction with formalin and primary amines gives pyrimidopyrimidines 11a–d via double Michael reactions.

Synthesis of 3-benzylxanthine and lumazine analogues

Several xanthines (7–13) are prepared by the cyclisation of 1-benzyl-5,6-diaminouracil with single-carbon inserting agents such as aromatic aldehydes, formamides, acetic anhydride, carbon disulfide, and nitrous acid. Treatment of 6-amino-1-benzyl-5-nitrosouracil with anilinobenzylidene derivatives (14–18) affords 7-hydroxyxanthines (19–23). Cyclisation of the diaminouracil 3 with glyoxal, benzil, and diethyl oxalate leads to lumazines (25–28).

SYNTHESIS OF NEW 4-ALKYLTHIAZOLO[5,4-D] PYRIMIDINE-1-OXIDES

Abstract 6-Chloro-1-methyluracil 1 was treated with various butyl and benzyl mercaptans to give 6-substituted-1-methyluracils 2a-d which were nitrated to yield the corresponding 5-nitro derivatives 3a-d. These were cyclized to 2-substituted-4-methylthiazolo[5,4-d] pyrimidine-5,7(4H)-dione-1-oxides 4a-c. On the other hand. the reaction of 6-chloro-5-nitro-1-pro-pyluracil 6 with the above mentioned reagents afforded 6-substituted-5-nitro-1-propyuracils 7a-d which were cyclized similarly to give the corresponding 2-substituted-4-propylthia-zolo[5,4-d]pyrirnidine-5,7 (4H)-dione-1-oxide derivatives 8a-d. The structures of these compounds were elucidated by 1H nmr, uv, mass spectra and elemental analysis.