BCR-ABL Inhibitors in Chronic Myeloid Leukemia: Process Chemistry and Biochemical Profile

被引：13

作者：

Leonetti, F. ^{[1
]}

Stefanachi, A. ^{[1
]}

Nicolotti, O. ^{[1
]}

Catto, M. ^{[1
]}

Pisani, L. ^{[1
]}

Cellamare, S. ^{[1
]}

Carotti, A. ^{[1
]}

机构：

[1] Univ Bari Aldo Moro, Dipartimento Farmacochim, I-70125 Bari, Italy

来源：

CURRENT MEDICINAL CHEMISTRY | 2011年 / 18卷 / 19期

关键词：

Chronic myeloid leukemia; BCR-ABL; tyrosine kinase inhibitors; T315I mutation; process chemistry; CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE INHIBITORS; 3-SUBSTITUTED BENZAMIDE DERIVATIVES; T315I GATEKEEPER MUTANT; ANTICANCER DRUG; CANCER-THERAPY; STRUCTURAL MECHANISM; IMATINIB RESISTANCE; SELECTIVE INHIBITOR; CHRONIC-PHASE;

D O I：

10.2174/092986711796150414

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2943 / 2959

页数：17

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