191338-96-2Relevant academic research and scientific papers
Design and Synthesis of Fragment Derivatives with a Unique Inhibition Mechanism of the uPAR·uPA Interaction
Bum-Erdene, Khuchtumur,Liu, Degang,Xu, David,Ghozayel, Mona K.,Meroueh, Samy O.
supporting information, p. 60 - 66 (2021/01/12)
There is substantial interest in the development of small molecules that inhibit the tight and highly challenging protein-protein interaction between the glycophosphatidylinositol (GPI)-anchored cell surface receptor uPAR and the serine protease uPA. While preparing derivatives of a fragment-like compound that previously emerged from a computational screen, we identified compound 5 (IPR-3242), which inhibited binding of uPA to uPAR with submicromolar IC50s. The high inhibition potency prompted us to carry out studies to rule out potential aggregation, lack of stability, reactivity, and nonspecific inhibition. We designed and prepared 16 derivatives to further explore the role of each substituent. Interestingly, the compounds only partially inhibited binding of a fluorescently labeled α-helical peptide that binds to uPAR at the uPAR·uPA interface. Collectively, the results suggest that the compounds bind to uPAR outside of the uPAR·uPA interface, trapping the receptor into a conformation that is not able to bind to uPA. Additional studies will have to be carried out to determine whether this unique inhibition mechanism can occur at the cell surface.
DIPHENYL OX-INDOL-2-ON COMPOUNDS AND THEIR USE IN THE TREATMENT OF CANCER
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Page/Page column 36, (2010/02/14)
The present invention relates to substituted 3,3-diphenyl-1,3-dihydro-indol-2-one compounds, and the use of such compounds for the preparation of a medicament for the treatment of cancer in a mammal. It is postulated that treatment of cancers in which inh
Ethyl (4-N-Acylaminopyridin-3-yl)glyoxylate and 5-Azaisatin as New Synthons for a Route to Various New Polyheterocycles
Rivalle, Christian,Bisagni, Emile
, p. 441 - 444 (2007/10/03)
From 4-N-protected-aminopyridines which were functionalized at their 3-position, 5-azaisatin and equivalent synthons where obtained. Via the use of the Pfitzinger reaction, these compounds provided an easy route to new and various polyheterocyclic compoun
