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3,5-二取代吲哚衍生物作为Pim激酶抑制剂的发现与评价

Discovery and evaluation of 3,5-disubstituted indole derivatives as Pim kinase inhibitors.

作者信息

More Kunal N, Hong Victor S, Lee Ahyeon, Park Jongsung, Kim Shin, Lee Jinho

机构信息

Department of Chemistry, Keimyung University, Daegu 42601, Republic of Korea.

Department of Immunology, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea.

出版信息

Bioorg Med Chem Lett. 2018 Aug 1;28(14):2513-2517. doi: 10.1016/j.bmcl.2018.05.054. Epub 2018 May 29.

Abstract

Pim kinases are promising therapeutic targets for the treatment of hematological cancers. A potent Pim kinase inhibitor 7f, derived from meridianin C, was further optimized by the replacement of 2-aminopyrimidine with substituted benzene. The optimization of the C-3 and C-5 positions of indole yielded compound 43 with improved cellular potency and high selectivity against a panel of 14 different kinases.

摘要

Pim激酶是治疗血液系统癌症很有前景的治疗靶点。一种源自meridianin C的强效Pim激酶抑制剂7f,通过用取代苯替换2-氨基嘧啶进行了进一步优化。对吲哚的C-3和C-5位进行优化得到了化合物43,其细胞活性得到改善,并且对14种不同激酶具有高选择性。

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