Design, synthesis and antitumor activity of novel pyrazolopyrimidine derivatives / Ahmed Ali Mohammed Ibrahim Elbatrawy ; Supervised Samir M. Elmoghazy , Riham F. George

Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutical Chemistry

In this thesis, novel series of pyrazolopyrimidines and pyrazolotriazolopyrimidine were designed. Molecular modelling techniques were used to support the design. 6-Substituted pyrazolo]3,4-d[pyrimidine derivatives IV, V, un/substituted benzylidene hydrazinyl derivatives VIa-c, benzohydrazide derivatives VIIa-c, pyrazolo[4,3-e][1,2,4]triazolo[4,3- a]pyrimidine derivatives IXa-c, Xa-c, XI, XIIa-c, XIII and XIVa,b were synthesized. Enzyme binding assay to Abelson tyrosine kinase (Abl) was carried out on most of the synthesized compounds. The most active derivatives as Abl inhibitors were further screened for their cytotoxic acitivity against leukemia K-562 cell line. The p-methoxy benzohydrazide VIIb and its unsubstituted derivative VIIa were the most active agents toward K-562 cytotoxicity assay with IC50 values of 0.05 and 0.07 æM, respectively. Moreover, all compounds were evaluated for their antitumor activity against colon HCT116 and vulvar epidermoid A431 cancer cell lines. Aim of the work The objective of this work was to design and synthesize new compounds as Abl inhibitors. The design of these compounds was based on the previous SAR studies of this class and supported by the molecular modelling technique.

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