| Title: |
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. |
| Authors: |
Tardy, S; Orsato, A; Mologni, L; Bisson, Wh; Donadoni, C; Gambacorti-Passerini, C; Scapozza, L; Gueyrard, D; Goekjian, Pg. |
| Contributors: |
Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon); Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS); Institut de Chimie Organique et Analytique (ICOA); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS); Chimie Organique 2-Glycochimie (CO2GLYCO); Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL) |
| Source: |
ISSN: 0968-0896. |
| Publisher Information: |
CCSD; Elsevier |
| Publication Year: |
2014 |
| Collection: |
Université d'Orléans: HAL |
| Subject Terms: |
Anaplastic lymphoma kinase; Kinase inhibitors; Aza-Graebe–Ullman; Regioselective cross coupling; Palladium catalyzed coupling; [CHIM.ORGA]Chemical Sciences/Organic chemistry |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1016/j.bmc.2014.01.007 |
| Availability: |
https://hal.science/hal-01147409; https://doi.org/10.1016/j.bmc.2014.01.007 |
| Accession Number: |
edsbas.FFE9D90B |
| Database: |
BASE |