Chromosomal translocations involving anaplastic lymphoma kinase (ALK) are the driving mutations for a range of cancers and ALK is thus considered an attractive therapeutic target. We synthesized a series of functionalized benzo[4,5]imidazo[1,2-c]pyrimidines and benzo[4,5]imidazo[1,2-a]pyrazines by an aza-Graebe-Ullman reaction, followed by palladium-catalyzed cross-coupling reactions. A sequential regioselective cross-coupling route is reported for the synthesis of unsymmetrically disubstituted benzo[4,5]imidazo[1,2-a]pyrazines. The inhibition of ALK was evaluated and compound 19 in particular showed good activity against both the wild type and crizotinib-resistant L1196M mutant in vitro and in ALK-transfected BaF3 cells.
Tardy, S., Orsato, A., Mologni, L., Bisson, W., Donadoni, C., Gambacorti Passerini, C., et al. (2014). Synthesis and biological evaluation of benzo[4,5]imidazo[1,2-c]pyrimidine and benzo[4,5]imidazo[1,2-a]pyrazine derivatives as anaplastic lymphoma kinase inhibitors. BIOORGANIC & MEDICINAL CHEMISTRY, 22(4), 1303-1312 [10.1016/j.bmc.2014.01.007].
Citazione: | Tardy, S., Orsato, A., Mologni, L., Bisson, W., Donadoni, C., Gambacorti Passerini, C., et al. (2014). Synthesis and biological evaluation of benzo[4,5]imidazo[1,2-c]pyrimidine and benzo[4,5]imidazo[1,2-a]pyrazine derivatives as anaplastic lymphoma kinase inhibitors. BIOORGANIC & MEDICINAL CHEMISTRY, 22(4), 1303-1312 [10.1016/j.bmc.2014.01.007]. | |
Tipo: | Articolo in rivista - Articolo scientifico | |
Carattere della pubblicazione: | Scientifica | |
Presenza di un coautore afferente ad Istituzioni straniere: | No | |
Titolo: | Synthesis and biological evaluation of benzo[4,5]imidazo[1,2-c]pyrimidine and benzo[4,5]imidazo[1,2-a]pyrazine derivatives as anaplastic lymphoma kinase inhibitors | |
Autori: | Tardy, S; Orsato, A; Mologni, L; Bisson, W; Donadoni, C; Gambacorti Passerini, C; Scapozza, L; Gueyrard, D; Goekjian, P | |
Autori: | ||
Data di pubblicazione: | 2014 | |
Lingua: | English | |
Rivista: | BIOORGANIC & MEDICINAL CHEMISTRY | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.bmc.2014.01.007 | |
Appare nelle tipologie: | 01 - Articolo su rivista |