Being the pyrazolo[3,4-d]pyrimidine ring system isoster with the adenine scaffold of ATP, many synthetic approaches for the construction of this bicyclic system have been developed in the last fifty years in order to identify novel bioactive molecules. The synthesis of 4-amino-pyrazolo[3,4-d]pyrimidine derivatives together with the functionalization of the core structure have been reviewed. The evolution of the scaffold from the pioneering work of Robins to the recent preparation of selective pharmacologically active molecules is discussed in terms of synthetic methodologies to produce biologically active compounds. With the literature on pyrazolo[3,4-d]pyrimidines particularly beings rich, the focus of this review deals with the construction of the ring system from pyrazoles only, reporting same selected examples in this branch of chemistry.
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