4336-70-3Relevant articles and documents
A Triazolotriazine-Based Dual GSK-3β/CK-1δ Ligand as a Potential Neuroprotective Agent Presenting Two Different Mechanisms of Enzymatic Inhibition
Redenti, Sara,Marcovich, Irene,De Vita, Teresa,Pérez, Concepción,De Zorzi, Rita,Demitri, Nicola,Perez, Daniel I.,Bottegoni, Giovanni,Bisignano, Paola,Bissaro, Maicol,Moro, Stefano,Martinez, Ana,Storici, Paola,Spalluto, Giampiero,Cavalli, Andrea,Federico, Stephanie
supporting information, p. 310 - 314 (2019/01/24)
Glycogen synthase kinase 3β (GSK-3β) and casein kinase 1δ (CK-1δ) are emerging targets for the treatment of neuroinflammatory disorders, including Parkinson's disease. An inhibitor able to target these two kinases was developed by docking-based design. Compound 12, 3-(7-amino-5-(cyclohexylamino)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-2-yl)-2-cyanoacrylamide, showed combined inhibitory activity against GSK-3β and CK-1δ [IC50(GSK-3β)=0.17 μm; IC50(CK-1δ)=0.68 μm]. In particular, classical ATP competition was observed against CK-1δ, and a co-crystal of compound 12 inside GSK-3β confirmed a covalent interaction between the cyanoacrylamide warhead and Cys199, which could help in the development of more potent covalent inhibitors of GSK-3β. Preliminary studies on in vitro models of Parkinson's disease revealed that compound 12 is not cytotoxic and shows neuroprotective activity. These results encourage further investigations to validate GSK-3β/CK-1δ inhibition as a possible new strategy to treat neuroinflammatory/degenerative diseases.
METHODS OF TREATING PULMONARY DISEASES AND DISORDERS
-
Paragraph 0133, (2017/07/14)
The present disclosure features disclosed method of treating disorders such as COPD, bronchitis and/or asthma using disclosed compounds, optionally together with one or more additional active agents. Contemplated methods include administrating orally or by inhalation to a patient one or more disclosed compounds.
Synthesis and antimicrobial activity of N-aryl-4-(cyano/alkoxycarbonyl)-5-(pyridin-3-yl)-1H/3H-1,2,3-triazole derivatives
Komsani, Jayaram Reddy,Avula, Sreenivas,Koppireddi, Satish,Koochana, Pranay Kumar,Usn, Murty,Yadla, Rambabu
, p. 764 - 772 (2015/05/13)
A convenient synthesis of a new series of N-aryl-5-(pyridin-3-yl)-1H/3H-1,2,3-triazole-4-carbonitriles and alkyl N-aryl-5-(pyridin-3-yl)-1H/3H-1,2,3-triazole-4-carboxylic acid esters is reported. The newly synthesized 5-(pyridin-3-yl)-1,2,3-triazole derivatives are evaluated for their antibacterial and antifungal activity. Some of these triazole derivatives have exhibited moderate antimicrobial activity.
