443799-31-3Relevant academic research and scientific papers
Selective Janus Kinase 2 (JAK2) Pseudokinase Ligands with a Diaminotriazole Core
Liosi, Maria-Elena,Krimmer, Stefan G.,Newton, Ana S.,Dawson, Thomas K.,Puleo, David E.,Cutrona, Kara J.,Suzuki, Yoshihisa,Schlessinger, Joseph,Jorgensen, William L.
, p. 5324 - 5340 (2020/06/10)
Janus kinases (JAKs) are non-receptor tyrosine kinases that are essential components of the JAK-STAT signaling pathway. Associated aberrant signaling is responsible for many forms of cancer and disorders of the immune system. The present focus is on the d
In silico Screening and Evaluation of Plasmodium falciparum Protein Kinase 5 (PK5) Inhibitors
Eubanks, Amber L.,Perkins, Marisha M.,Sylvester, Kayla,Ganley, Jack G.,Posfai, Dora,Sanschargrin, Paul C.,Hong, Jiyong,Sliz, Piotr,Derbyshire, Emily R.
supporting information, p. 2479 - 2483 (2018/11/23)
An in silico screen of 350 000 commercially available compounds was conducted with an unbiased approach to identify potential malaria inhibitors that bind to the Plasmodium falciparum protein kinase 5 (PfPK5) ATP-binding site. PfPK5 is a cyclin-dependent kinase-like protein with high sequence similarity to human cyclin-dependent kinase 2 (HsCDK2), but its precise role in cell-cycle regulation remains unclear. After two-dimensional fingerprinting of the top scoring compounds, 182 candidates were prioritized for biochemical testing based on their structural diversity. Evaluation of these compounds demonstrated that 135 bound to PfPK5 to a similar degree or better than known PfPK5 inhibitors, confirming that the library was enriched with PfPK5-binding compounds. A previously reported triazolodiamine HsCDK2 inhibitor and the screening hit 4-methylumbelliferone were each selected for an analogue study. The results of this study highlight the difficult balance between optimization of PfPK5 affinity and binding selectivity for PfPK5 over its closest human homologue HsCDK2. Our approach enabled the discovery of several new PfPK5-binding compounds from a modest screening campaign and revealed the first scaffold to have improved PfPK5/HsCDK2 selectivity. These steps are critical for the development of PfPK5-targeting probes for functional studies and antimalarials with decreased risks of host toxicity.
TRIAZOLE COMPOUNDS AS ANTIVIRALS
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Paragraph 0213, (2014/01/18)
The present invention discloses compounds of Formula I: wherein the variables in Formula I are defined as described herein. Also disclosed are pharmaceutical compositions containing such compounds and methods for using the compounds of Formula I in the prevention or treatment of HCV infection.
Diamino-1,2,4-triazole derivatives are selective inhibitors of TYK2 and JAK1 over JAK2 and JAK3
Malerich, Jeremiah P.,Lam, Jennifer S.,Hart, Barry,Fine, Richard M.,Klebansky, Boris,Tanga, Mary J.,D'Andrea, Annalisa
scheme or table, p. 7454 - 7457 (2011/01/12)
Tyrosine kinase 2 (TYK2) is required for signaling of interleukin-23 (IL-23), which plays a key role in rheumatoid arthritis. Presented is the design and synthesis of 1,2,4-triazoles, and the evaluation of their inhibitory activity against the Janus associated kinases TYK2 and JAKs 1-3.
1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: Synthesis and evaluation of biological activities
Lin, Ronghui,Connolly, Peter J.,Huang, Shenlin,Wetter, Steven K.,Lu, Yanhua,Murray, William V.,Emanuel, Stuart L.,Gruninger, Robert H.,Fuentes-Pesquera, Angel R.,Rugg, Catherine A.,Middleton, Steven A.,Jolliffe, Linda K.
, p. 4208 - 4211 (2007/10/03)
A series of 1-acyl-1H-[1,2,4]triazole-3,5-diamine analogues were synthesized as cyclin-dependent kinase (CDK) inhibitors. These compounds showed potent and selective CDK1 and CDK2 inhibitory activities and inhibited in vitro cellular proliferation in various human tumor cells. Representative compound 3b demonstrated in vivo efficacy in a human melanoma A375 xenograft model in nude mice.
