Discovery of a potent tyrosine kinase AXL inhibitor bearing the 3-((2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)amino)pyrazine core.

Wang, Yueliang; Xing, Li; Ji, Yinchun; Ye, Jiqing; Dai, Yang; Gu, Wangting; Ai, Jing; Song, Zilan

Wang, Yueliang; Xing, Li; Ji, Yinchun; Ye, Jiqing; Dai, Yang; Gu, Wangting; Ai, Jing; Song, Zilan.

Affiliation

Wang Y; Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai 200444, China; Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.
Xing L; CAS Key Laboratory of Receptor Research and the State Key Laboratory for Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.
Ji Y; Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.
Ye J; CAS Key Laboratory of Receptor Research and the State Key Laboratory for Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.
Dai Y; Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.
Gu W; CAS Key Laboratory of Receptor Research and the State Key Laboratory for Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.
Ai J; Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: jai@simm.ac.cn.
Song Z; CAS Key Laboratory of Receptor Research and the State Key Laboratory for Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: songalan@simm.ac.cn.

Bioorg Med Chem Lett ; 29(6): 836-838, 2019 03 15.

Article de En | MEDLINE | ID: mdl-30685094

ABSTRACT

ABSTRACT

Starting from the recently launched FLT3/AXL multi-targeted inhibitor Gilteritinib (5), we conducted a side-chain ring closure medicinal chemistry approach leading to the identification of compound 15c as a highly potent AXL inhibitor in the biochemical and cellular anti-proliferative assays, with IC50 values of 1.2 and 0.3â¯nM, respectively. Compared with the reference compound 5, our new discovered AXL inhibitor 15c is more potent in both assays.

Sujet(s)
Mots clés

AXL Kinase; Cancer; Pyrazine

Texte intégral

Ajouter à My VHL

Imprimer

XML

PubMed Links

Recherche sur Google

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Pyrazines / Benzazépines / Récepteurs à activité tyrosine kinase / Inhibiteurs de protéines kinases Limites: Animals Langue: En Journal: Bioorg Med Chem Lett Sujet du journal: BIOQUIMICA / QUIMICA Année: 2019 Type de document: Article Pays d'affiliation: Chine

Texte intégral

Ajouter à My VHL

Imprimer

XML

PubMed Links

Recherche sur Google