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].

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

ORSATO, ALEXANDRE;MOLOGNI, LUCA;DONADONI, CARLA;GAMBACORTI PASSERINI, CARLO;
2014

Abstract

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.
No
Articolo in rivista - Articolo scientifico
Scientifica
Kinase inhibitors; Regioselective cross coupling; Aza-Graebe–Ullman; Palladium catalyzed coupling; Anaplastic lymphoma kinase
English
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].
Tardy, S; Orsato, A; Mologni, L; Bisson, W; Donadoni, C; GAMBACORTI PASSERINI, C; Scapozza, L; Gueyrard, D; Goekjian, P
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/52073
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