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Design and Synthesis of Thiadiazoles and Thiazoles Targeting the Bcr‐Abl T315I Mutant: from Docking False Positives to ATP‐Noncompetitive Inhibitors
Author(s) -
Radi Marco,
Crespan Emmanuele,
Falchi Federico,
Bernardo Vincenzo,
Zanoli Samantha,
Manetti Fabrizio,
Sche Silvia,
Maga Giovanni,
Botta Maurizio
Publication year - 2010
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000066
Subject(s) - mutant , thiadiazoles , allosteric regulation , computational biology , docking (animal) , computer science , chemistry , biochemistry , biology , enzyme , medicinal chemistry , medicine , gene , nursing
Overcoming resistance: In an effort to optimize our previously identified dual Src/Abl hits, a new series of 1,3,4‐thiadiazoles and 1,3‐thiazoles were designed and synthesized, paying particular attention to the reduction of their lipophilicity and to the improvement of the affinity towards the drug‐resistant T315I mutant. Compound 5 was identified as a promising allosteric inhibitor of the T315I mutant.