Discovery and SAR of 1,3,4-thiadiazole derivatives as potent Abl tyrosine kinase inhibitors and cytodifferentiating agents.

Description

A series of substituted benzoylamino-2-[(4-benzyl)thio]-1,3,4-thiadiazoles has been discovered as potent Abl tyrosine kinase inhibitors. Mol. docking simulations on the Abl tyrosine kinase were conducted to rationalize the SAR of the synthesized inhibitors. The most active compd. identified from the enzymic screening (6a) showed interesting inhibitory activity on Imatinib-sensitive murine myeloid 3B clone and Bcr-Abl-independent Imatinib-resistant leukemia cells. Surprisingly, 6a was also proved to act as differentiating inducers in human promyelocytic leukemia cells (HL-60).

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