Fused heterocyclic derivatives with thiazole moiety are very prospective objects in modern drug discovery. Isomer [4,5-d] of thiazolopyrimidines can be considered as a 7-thia-analogue of the naturally occurring purine bases, adenine and guanine and have been reported to possess broad spectrum of activities . Futhermore, based on the fact that many Schiff's bases and hydrazones exert potential anticancer acitivity we we planned to synthesize a series of novel thiazolo[4,5-d]-pyrimidine derivatives as an interesting structure, especially as potential antitumor agents. The presence of fluorine often increases the lipid solubility and therapeutic efficiacy of a drug. We introduced fluorophenyl moiety into 2 and 7 positions of the prepared compunds. We described methods developed to synthesize and modify the structure of the thiazolo[4,5-d]pyrimidine ring system with hope of discovering biologically active, selective and less toxic compounds. The synthetic strategies adopted to obtain the target compounds are depicted in Schemes 1 and 2.

The necessary aminothiazole compound 1 was prepared by reacting phenyl isothiocyanate with powdered sulphur and methyl cyanoacetate in the presence of triethylamine. Treatment of aminothiazole with dimethylsulphate for the replacment of the 2-tioxo group with an active methylene moiety followed by reaction of the produced 2-methylthiothiazolium salt with hydrazine hydrate gave the 2-hydrazonoderivative. This compound was cyclized to the thiazolo[4,5-d]pyrimidine using a benzaldehyde. The intermediate 2-methylthiothiazolium salt with the various amines, especially 4-fluoroaniline, gave 2-iminoderivatives which were cyclized to bicyclic system under the same conditions as described above.

The second parent thiazolo[4,5-d]pyrimidine substituted at position 7 was prepared by cyclization of aminothiazole with benzaldehyde, but the reaction required the presence of a basic catalyst. Chlorination of products with phosphorus oxychloride gave 7-chlorothiazolo[4,5-d]pyrimidine which upon treatment with amines gave the 7-aminoderivatives. The replactment of 7-chloro with 7-hydrazino group by using hydrazine hydrate gave 7-hydrazinothiazolo[4,5-d]pyrimidine derivative. Condensation of the latter compound with benzaldehyde yielded 7-benzylidenehydrazino derivative.

The structures of prepared compounds were confirmed by elemental analysis, IR, ¹HNMR. They will be evaluated for their anticancer activity in the NCI screening program.

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1. New 4,8-dihydroxy-1-oxo-6-phenyl-1,2-dihydro-2,7-naphthyridine-3-carboxylate derivatives with potential anticancer activity
2. Synthesis and in vitro anticancer evaluation of the new thiazolo[4,5-d]pyrimidines.
3. Synthesis and antitumor activity of novel 6-phenyl-2,7-naphthyridine derivatives.