1111235-07-4Relevant academic research and scientific papers
The discovery and optimization of novel dual inhibitors of topoisomerase ii and histone deacetylase
Zhang, Xuan,Bao, Bin,Yu, Xiuhua,Tong, Linjiang,Luo, Yu,Huang, Qingqing,Su, Mingbo,Sheng, Li,Li, Jia,Zhu, Hong,Yang, Bo,Zhang, Xiongwen,Chen, Yi,Lu, Wei
, p. 6981 - 6995 (2013)
A novel class of podophyllotoxin derivatives have been designed and synthesized based on the synergistic antitumor effects of topoisomerase II and histone deacetylase inhibitors. Their inhibitory activities towards histone deacetylases and Topo II and their cytotoxicities in cancer cell lines were evaluated. The aromatic capping group connection, linker length and zinc-binding group were systematically varied and preliminary conclusions regarding structure-activity relationships are discussed. Among all of the synthesized hybrid compounds, compound 24d showed the most potent HDAC inhibitory activity at a low nanomolar level and exhibited powerful antiproliferative activity towards HCT116 colon carcinoma cells at a low micromolar level. Further exploration of this series led to the discovery of potent dual inhibitor 32, which exhibited the strongest in vitro cytotoxic activity.
PYRROLOPYRIMIDINES
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Page/Page column 50, (2009/03/07)
The present invention relates to compounds or pharmaceutically-acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to compounds that are polo-like kinase (PLKs) inhibitors useful for the treatment of disease states mediated by PLK, especially PLK4, in particular such compounds that are useful in the treatment of pathological processes which involve an aberrant cellular proliferation, such as tumour growth, rheumatoid arthritis, restenosis and atherosclerosis.
