| Literature DB >> 26739779 |
Biao Lu1, Hu Cao1, Jingsong Cao2, Song Huang1, Qiyue Hu1, Dong Liu2, Ru Shen2, Xiaodong Shen1, Weikang Tao1, Hong Wan1, Dan Wang1, Yinfa Yan2, Liuqing Yang2, Jiayin Zhang2, Lei Zhang1, Lianshan Zhang3, Minsheng Zhang2.
Abstract
A novel series of pyrazolo[3,4-c]isoquinoline derivatives was discovered as B-Raf(V600E) inhibitors through scaffold hopping based on a literature lead PLX4720. Further SAR exploration and optimization led to the discovery of potent B-Raf(V600E) inhibitors with good oral bioavailability in rats and dogs. One of the compounds EBI-907 (13g) demonstrated excellent in vivo efficacy in B-Raf(V600E) dependent Colo-205 tumor xenograft models in mouse and is under preclinical studies for the treatment of melanoma and B-Raf(V600E) associated cancers.Entities:
Keywords: B-Raf(V600E); Cancer; Kinase; Pyrazolo[3,4-c]isoquinoline; Scaffold hopping
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Year: 2015 PMID： 26739779 DOI： 10.1016/j.bmcl.2015.12.086
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823