title: Discovery and SAR of 1,3,4-thiadiazole derivatives as potent Abl tyrosine kinase inhibitors and cytodifferentiating agents.
abstract: A series of substituted benzoylamino-2-[(4-benzyl)thio]-1,3,4-thiadiazoles has been discovered as potent Abl tyrosine kinase inhibitors. Molecular docking simulations on the Abl tyrosine kinase were conducted in order to rationalize the SAR of the synthesized inhibitors. The most active compound identified from the enzymatic 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).
authors: Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via Alcide de Gasperi 2, I-53100 Siena, Italy.
authors: Marco
authors: M
authors: Radi
authors: Emmanuele
authors: E
authors: Crespan
authors: Giorgia
authors: G
authors: Botta
authors: Federico
authors: F
authors: Falchi
authors: Giovanni
authors: G
authors: Maga
authors: Fabrizio
authors: F
authors: Manetti
authors: Valentina
authors: V
authors: Corradi
authors: Manuela
authors: M
authors: Mancini
authors: Maria Alessandra
authors: MA
authors: Santucci
authors: Silvia
authors: S
authors: Schenone
authors: Maurizio
authors: M
authors: Botta
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors*; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D054852:Small Molecule Libraries; D013830:Thiadiazoles; D016315:Proto-Oncogene Proteins c-abl