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 microg/ml, respectively. On the other hand, compound 5 showed significant radioprotective effect.

Synthesis, anticancer and radioprotective activities of some new pyrazolo[3,4-d]pyrimidines containing amino acid moieties.

Various isomeric structural purine analogues possessing the pyrazolo[3,4-d]pyrimidine nucleus bearing amino acid moieties have been synthesized. The structures of the synthesized compounds were elucidated by spectral data. Preliminary testing for in vitro anticancer activity of the synthesized compounds against Ehrlich ascites carcinoma cells was carried out. 2-(1-Phenyl-1H-pyrazolo [3,4-d]pyrimidin-4-ylamino)-propanoic acid (3 d), 4-methyl-2-(1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-ylamino)-pentanoic acid (3 d), 4-methylthlo-2-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)-butanoic acid (3e) and phenyl-2-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)propanoic acid (3f) were the most active compounds. Moreover, compounds 3e and 1-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-pyrrolidine-2-carboxylic acid (4) exhibited significant in vivo radioprotective activity.