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  • Design and synthesis of a highly selective, orally active and potent anaplastic lymphoma kinase inhibitor (CH5424802).

Design and synthesis of a highly selective, orally active and potent anaplastic lymphoma kinase inhibitor (CH5424802).

Bioorganic & medicinal chemistry (2012-01-10)
Kazutomo Kinoshita, Kohsuke Asoh, Noriyuki Furuichi, Toshiya Ito, Hatsuo Kawada, Sousuke Hara, Jun Ohwada, Takuho Miyagi, Takamitsu Kobayashi, Kenji Takanashi, Toshiyuki Tsukaguchi, Hiroshi Sakamoto, Takuo Tsukuda, Nobuhiro Oikawa
ABSTRACT

Anaplastic lymphoma kinase (ALK) receptor tyrosine kinase is considered an attractive therapeutic target for human cancers, especially non-small cell lung cancer (NSCLC). Our previous study revealed that 8,9-side-chains of 6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole scaffold crucially affected kinase selectivity, cellular activity, and metabolic stability. In this work, we optimized the side-chains and identified highly selective, orally active and potent ALK inhibitor CH5424802 (18a) as the clinical candidate.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
N-Boc-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester, 95%