title: BCR-ABL inhibitors in chronic myeloid leukemia: process chemistry and biochemical profile.
abstract: 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.
authors.affiliation: Dipartimento Farmacochimico, Università degli Studi di Bari Aldo Moro, via Orabona, 4, I-70125, Bari, Italy. fleonetti@farmchim.uniba.it
authors.forename: F
authors.initials: F
authors.lastname: Leonetti
authors.forename: A
authors.initials: A
authors.lastname: Stefanachi
authors.forename: O
authors.initials: O
authors.lastname: Nicolotti
authors.forename: M
authors.initials: M
authors.lastname: Catto
authors.forename: L
authors.initials: L
authors.lastname: Pisani
authors.forename: S
authors.initials: S
authors.lastname: Cellamare
authors.forename: A
authors.initials: A
authors.lastname: Carotti
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl