240117-34-4Relevant academic research and scientific papers
Structure-activity relationship and improved hydrolytic stability of pyrazole derivatives that are allosteric inhibitors of West Nile Virus NS2B-NS3 proteinase
Sidique, Shyama,Shiryaev, Sergey A.,Ratnikov, Boris I.,Herath, Ananda,Su, Ying,Strongin, Alex Y.,Cosford, Nicholas D.P.
scheme or table, p. 5773 - 5777 (2010/04/30)
West Nile Virus (WNV) is a potentially deadly mosquito-borne flavivirus which has spread rapidly throughout the world. Currently there is no effective vaccine against flaviviral infections. We previously reported the identification of pyrazole ester derivatives as allosteric inhibitors of WNV NS2B-NS3 proteinase. These compounds degrade rapidly in pH 8 buffer with a half life of 1-2 h. We now report the design, synthesis and in vitro evaluation of pyrazole derivatives that are inhibitors of WNV NS2B-NS3 proteinase with greatly improved stability in the assay medium.
Identification and characterization of 3-substituted pyrazolyl esters as alternate substrates for cathepsin B: The confounding effects of DTT and cysteine in biological assays
Myers, Michael C.,Napper, Andrew D.,Motlekar, Nuzhat,Shah, Parag P.,Chiu, Chun-Hao,Beavers, Mary Pat,Diamond, Scott L.,Huryn, Donna M.,Smith III, Amos B.
, p. 4761 - 4766 (2008/02/11)
Substituted pyrazole esters were identified as hits in a high throughput screen (HTS) of the NIH Molecular Libraries Small Molecule Repository (MLSMR) to identify inhibitors of the enzyme cathepsin B. Members of this class, along with functional group analogs, were synthesized in an effort to define the structural requirements for activity. Analog characterization was hampered by the need to include a reducing agent such as dithiothreitol (DTT) or cysteine in the assay, highlighting the caution required in interpreting biological data gathered in the presence of such nucleophiles. Despite the confounding effects of DTT and cysteine, our studies demonstrate that the pyrazole 1 acts as alternate substrate for cathepsin B, rather than as an inhibitor.
Novel synthesis of 5-amino-1-arylsulfonyl-4-pyrazolin-3-ones as a new class of N-sulfonylated pyrazoles
Elgemeie, Galal H.,Metwally, Nadia H.
, p. 384 - 385 (2007/10/03)
A novel synthesis of 5-amino-1-arylsulfonyl-4-pyrazolin-3-ones via intramolecular cyclization of cyanoaceto-N-arylsulfonylhydrazides is reported and the synthetic potential of the method is demonstrated.
