发明名称 |
COMPOUNDS WHICH INHIBIT RNA POLYMERASE, COMPOSITIONS INCLUDING SUCH COMPOUNDS, AND THEIR USE |
摘要 |
RNA polymerase I (Pol I) is a dedicated polymerase for the transcription of the 47S ribosomal RNA precursor subsequently processed into the mature 5.8S, 18S and 28S ribosomal RNAs and assembled into ribosomes in the nucleolus. Pol I activity is commonly deregulated in human cancers. Based on the discovery of lead molecule BMH-21, a series of pyridoquinazolinecarboxamides were synthesized as inhibitors of Pol I and activators of the destruction of RPA194, the Pol I large catalytic subunit protein. The present invention identifies a set of bioactive compounds, including purified stereoisomers, that potently cause RPA194 degradation that function in a tightly constrained chemical space. Pharmaceutical compositions comprising these compounds and their uses in cancer and other Pol I related diseases is also provided. |
申请公布号 |
EP3119781(A1) |
申请公布日期 |
2017.01.25 |
申请号 |
EP20150765295 |
申请日期 |
2015.03.20 |
申请人 |
The Johns Hopkins University;Lieber Institute For Brain Development |
发明人 |
LAIHO, Marikki;COLIS, Laureen;BARROW, James C.;ERNST, Glen;SANDERS, Sarah |
分类号 |
C07D471/04;A61K31/4375;A61K31/519;A61P35/00;C07D401/12;C07D403/12;C07D487/04 |
主分类号 |
C07D471/04 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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