Synthesis of some new pyrazolo[3,4-d]pyrimidine derivatives of expected anticancer and radioprotective activity

On the account of the reported anticancer activity of pyrazolo[3,4-d]pyrimidines, a new series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized and tested for in-vitro anticancer activity against Ehrlich Ascites Carcinoma (EAC) cell line. Moreover, one of the target products was evaluated for in-vivo radioprotective activity.The reaction of o-aminoester 1 with benzylamine in presence of triethylorthoformate yielded the corresponding 5-benzylpyrazolopyrimidine derivative 2. The N-amino derivative 3 was used to synthesize new derivatives of pyrazolopyrimidines 4–7. The corresponding 1,3,4-oxadiazolopyrazolopyrimidine derivatives 12 and 14 were obtained via reaction of compound 9 with reagent 10 and/or triethylorthoformate. Thiophosgenation of compound 1 furnished the corresponding 5-isothiocyanate derivative 15, which was reacted with o-phenylenediamine, thiosemicarbazide and anthranilic acid to give benzimidazolopyrazolopyrimidine, 17, pyrazolotriazolopyrimidine, 19 and pyrazolopyrimidobenzoxazine, 20 respectively. The structures of the synthesized compounds were confirmed by microanalyses, IR, NMR, and mass spectral data.Compounds 2 and 9 showed intermediate anticancer activity compared to doxorubicin as positive control with IC50 values of 90 and 100 μg/ml, respectively. On the other hand, compound 5 showed significant radioprotective effect.

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