Exploring the Chemical Space around the Privileged Pyrazolo[3,4‑<i>d</i>]pyrimidine Scaffold: Toward Novel Allosteric Inhibitors of T315I-Mutated Abl Giulia Vignaroli Martina Mencarelli Deborah Sementa Emmanuele Crespan Miroslava Kissova Giovanni Maga Silvia Schenone Marco Radi Maurizio Botta 10.1021/co500004e.s001 https://acs.figshare.com/articles/journal_contribution/Exploring_the_Chemical_Space_around_the_Privileged_Pyrazolo_3_4_i_d_i_pyrimidine_Scaffold_Toward_Novel_Allosteric_Inhibitors_of_T315I_Mutated_Abl/2306203 A library of pyrazolo­[3,4-<i>d</i>]­pyrimidines, endowed with a high level of molecular diversity, has been developed applying a synthetic sequence that allowed C3, N1, C4, and C6 substitution. The enzymatic screening of this “privileged scaffold”-based compound collection, validated the use of a diversity-oriented approach in a field characteristically explored by target-oriented synthesis. In fact, several compounds showed high activity against the selected kinases (i.e., Src, Abl <i>wt</i>, and T315I mutated-form), furthermore and interestingly a new compound has emerged as an allosteric inhibitor of the T315I mutated-form of Abl, opening up new opportunities for the development of a novel class of noncompetitive inhibitors of Abl (T315I). 2014-04-14 00:00:00 C 6 substitution Abl wt Novel Allosteric Inhibitors compound T 315I AblA library allosteric inhibitor Chemical Space novel class