A library of pyrazolo[3,4-d]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 wt, 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).

Vignaroli, G., Mencarelli, M., Sementa, D., Crespan, E., Kissova, M., Maga, G., et al. (2014). Exploring the chemical space around the privileged pyrazolo[3,4-d]pyrimidine scaffold: toward novel allosteric inhibitors of T315I-mutated Abl. ACS COMBINATORIAL SCIENCE, 16(4), 168-175 [10.1021/co500004e].

Exploring the chemical space around the privileged pyrazolo[3,4-d]pyrimidine scaffold: toward novel allosteric inhibitors of T315I-mutated Abl.

VIGNAROLI, GIULIA;SEMENTA, DEBORAH;BOTTA, MAURIZIO;
2014-01-01

Abstract

A library of pyrazolo[3,4-d]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 wt, 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).
Vignaroli, G., Mencarelli, M., Sementa, D., Crespan, E., Kissova, M., Maga, G., et al. (2014). Exploring the chemical space around the privileged pyrazolo[3,4-d]pyrimidine scaffold: toward novel allosteric inhibitors of T315I-mutated Abl. ACS COMBINATORIAL SCIENCE, 16(4), 168-175 [10.1021/co500004e].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/49548
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