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.
Design and Synthesis of Thiadiazoles and Thiazoles Targeting the Bcr-Abl T315I Mutant: from Docking False Positives to ATP-Noncompetitive Inhibitors / Marco Radi;Emmanuele Crespan;Federico Falchi;Vincenzo Bernardo;Samantha Zanoli;Fabrizio Manetti;Silvia Schenone;Giovanni Maga;Maurizio Botta. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 5(2010), pp. 1226-1231. [10.1002/cmdc.201000066]