F. Leonetti, A. Stefanachi, O. Nicolotti, M. Catto, L. Pisani, S. Cellamare and A. Carotti Pages 2943 - 2959 ( 17 )
Chronic myeloid leukemia (CML) is a myeloproliferative disease originating from a constitutively active tyrosine kinase, called BCR-ABL, expressed by an oncogene resulting from a reciprocal translocation between chromosome 9 and chromosome 22, coded as (t[9,22][q34;q11]). Inhibition of BCR-ABL with tyrosine kinase inhibitors (TKI) proved to be an efficient targeted therapy of Philadelphia-positive (Ph+) CML in the chronic phase. This review mainly addresses the synthetic pathways and process chemistry leading to the large scale preparation for pre-clinical demands and clinical supply of the three TKIs approved for Ph+ CML, i.e., imatinib, dasatinib and nilotinib and three more investigational drugs, i.e., bosutinib, ponatinib and bafetinib. Recent progress on the biochemical profiling of the six examined TKIs has been also reported.
Chronic myeloid leukemia,BCR-ABL,tyrosine kinase inhibitors,T315I mutation,process chemistry
, , , , , , Dipartimento Farmacochimico, Universita degli Studi di Bari “Aldo Moro”, via Orabona, 4, I-70125, Bari, Italy.