4393-98-0Relevant academic research and scientific papers
SYNTHESIS, ANTI-INFLAMMATORY AND ANALGESIC ACTIVITY OF PYRIDOQUINAZOLINE DERIVATIVES
Mikhalev, A. I.,Kon'shin, M. E.,Ovodenko, L. A.,Zaks, A. S.
, p. 124 - 126 (1995)
Derivatives of pyridoquinazoline were synthesized by reacting 2-chloronicotinic acid, its nitrile and amides with anthranilic acid or 2-aminotriphenylcarbinol.The anti-inflammatory and analgesic activity of the compounds was studied.
CARBOXYLIC ACID DERIVATIVES OF PYRIDOQUINAZOLINES USEFUL AS PROTEIN KINASE INHIBITORS
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Paragraph 0234-0237, (2020/04/09)
The present invention relates to novel carboxylic acid derivatives of 11-oxo-11H-pyrido [2,1-b]quinazoline-6-carboxamide as potent inhibitors of protein kinase, to pharmaceutical compositions containing them and to the use of said compounds for the manufa
COMPOUNDS WHICH INHIBIT RNA POLYMERASE, COMPOSITIONS INCLUDING SUCH COMPOUNDS, AND THEIR USE
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Paragraph 0083, (2015/11/10)
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.
Design, synthesis, and structure-activity relationships of pyridoquinazolinecarboxamides as RNA polymerase i inhibitors
Colis, Laureen,Ernst, Glen,Sanders, Sara,Liu, Hester,Sirajuddin, Paul,Peltonen, Karita,Depasquale, Michael,Barrow, James C.,Laiho, Marikki
, p. 4950 - 4961 (2014/07/07)
RNA polymerase I (Pol I) is a dedicated polymerase that transcribes the 45S ribosomal (r) RNA precursor. The 45S rRNA precursor is subsequently processed into the mature 5.8S, 18S, and 28S rRNAs and assembled into ribosomes in the nucleolus. Pol I activity is commonly deregulated in human cancers. On the basis of the discovery of lead molecule BMH-21, a series of pyridoquinazolinecarboxamides have been evaluated as inhibitors of Pol I and activators of the destruction of RPA194, the Pol I large catalytic subunit protein. Structure-activity relationships in assays of nucleolar stress and cell viability demonstrate key pharmacophores and their physicochemical properties required for potent activation of Pol I stress and cytotoxicity. This work identifies a set of bioactive compounds that potently cause RPA194 degradation that function in a tightly constrained chemical space. This work has yielded novel derivatives that contribute to the development of Pol I inhibitory cancer therapeutic strategies.
