title: N-[2-Methyl-5-(triazol-1-yl)phenyl]pyrimidin-2-amine as a scaffold for the synthesis of inhibitors of Bcr-Abl.
abstract: N-[2-Methyl-5-(triazol-1-yl)phenyl]pyrimidin-2-amine derivatives were synthesized and evaluated in vitro for their potential use as inhibitors of Bcr-Abl. The design is based on the bioisosterism between the 1,2,3-triazole ring and the amide group. The synthesis involves a copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) as the key step, with the exclusive production of anti-(1,4)-triazole derivatives. One of the compounds obtained shows general activity similar to that of imatinib; in particular, it was observed to be more effective in decreasing the fundamental function of cdc25A phosphatases in the K-562 cell line.
authors: Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milan, Via G. Venezian 21, 20133 Milano, Italy.
authors: Federica
authors: F
authors: Arioli
authors: Stella
authors: S
authors: Borrelli
authors: Francesco
authors: F
authors: Colombo
authors: Federico
authors: F
authors: Falchi
authors: Irene
authors: I
authors: Filippi
authors: Emmanuele
authors: E
authors: Crespan
authors: Antonella
authors: A
authors: Naldini
authors: Giusy
authors: G
authors: Scalia
authors: Alessandra
authors: A
authors: Silvani
authors: Giovanni
authors: G
authors: Maga
authors: Fabio
authors: F
authors: Carraro
authors: Maurizio
authors: M
authors: Botta
authors: Daniele
authors: D
authors: Passarella
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D020128:Inhibitory Concentration 50; D020014:K562 Cells / Q000201:enzymology; D008958:Models, Molecular; D009154:Mutation; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology; D050799:STAT5 Transcription Factor / Q000378:metabolism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry; D051028:bcl-2-Associated X Protein / Q000235:genetics; D051020:bcl-X Protein / Q000235:genetics; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C494811:BCL2L1 protein, human; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D050799:STAT5 Transcription Factor; D014230:Triazoles; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D019061:src-Family Kinases; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases