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Bioorg Med Chem Lett. 2015 Sep 15;25(18):3992-8. doi: 10.1016/j.bmcl.2015.07.004. Epub 2015 Jul 17.

Synthesis and evaluation of novel 2,4-diaminopyrimidines bearing bicyclic aminobenzazepines for anaplastic lymphoma kinase (ALK) inhibitor.

Author information

1
Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
2
Department of Chemistry, Korea University, Seoul 136-701, Republic of Korea.
3
College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 362-763, Republic of Korea.
4
Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea; Department of Medicinal Chemistry and Pharmacology, University of Science & Technology, Daejeon 305-550, Republic of Korea.
5
Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea. Electronic address: hyngrk@krict.re.kr.
6
Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea; Department of Medicinal Chemistry and Pharmacology, University of Science & Technology, Daejeon 305-550, Republic of Korea. Electronic address: jyhwang@krict.re.kr.

Abstract

A series of novel 2,4-diaminopyrimidine compounds bearing bicyclic aminobenzazepine were synthesized and evaluated for their anti-ALK activities. The activities of these compounds were confirmed in both enzyme- and cell-based ALK assays. Amongst compounds synthesized, KRCA-0445 showed very promising results in pharmacokinetic study and in vivo efficacy study with H3122 xenograft mouse model.

KEYWORDS:

2,4-Diaminopyrimidine; ALK; Cancer

PMID:
26235945
DOI:
10.1016/j.bmcl.2015.07.004
[Indexed for MEDLINE]

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