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