431-38-9Relevant articles and documents
BICYCLIC JAK INHIBITORS AND USES THEREOF
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Paragraph 000322, (2020/10/20)
Provided herein are compounds of Formulas (I), (II), (III), and (IV) and subformulas thereof, wherein the variables are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I), (II), (III), or (IV) and methods of using the compounds, e.g., in the treatment of immune disorders, inflammatory disorders, and cancer.
Development of Fragment-Based n-FABS NMR Screening Applied to the Membrane Enzyme FAAH
Lambruschini, Chiara,Veronesi, Marina,Romeo, Elisa,Garau, Gianpiero,Bandiera, Tiziano,Piomelli, Daniele,Scarpelli, Rita,Dalvit, Claudio
, p. 1611 - 1619 (2013/09/23)
Despite the recognized importance of membrane proteins as pharmaceutical targets, the reliable identification of fragment hits that are able to bind these proteins is still a major challenge. Among different 19F NMR spectroscopic methods, n-fluorine atoms for biochemical screening (n-FABS) is a highly sensitive technique that has been used efficiently for fragment screening, but its application for membrane enzymes has not been reported yet. Herein, we present the first successful application of n-FABS to the discovery of novel fragment hits, targeting the membrane-bound enzyme fatty acid amide hydrolase (FAAH), using a library of fluorinated fragments generated based on the different local environment of fluorine concept. The use of the recombinant fusion protein MBP-FAAH and the design of compound 11 as a suitable novel fluorinated substrate analogue allowed n-FABS screening to be efficiently performed using a very small amount of enzyme. Notably, we have identified 19 novel fragment hits that inhibit FAAH with a median effective concentration (IC50) in the low mM-μM range. To the best of our knowledge, these results represent the first application of a 19F NMR fragment-based functional assay to a membrane protein.
Design, synthesis, and evaluation of trifluoromethyl ketones as inhibitors of SARS-CoV 3CL protease
Shao, Yi-Ming,Yang, Wen-Bin,Kuo, Tun-Hsun,Tsai, Keng-Chang,Lin, Chun-Hung,Yang, An-Suei,Liang, Po-Huang,Wong, Chi-Huey
, p. 4652 - 4660 (2008/12/20)
A series of trifluoromethyl ketones as SARS-CoV 3CL protease inhibitors was developed. The inhibitors were synthesized in four steps from commercially available compounds. Three different amino acids were explored in the P1-position and in the P2-P4 positions varying amino acids and long alkyl chain were incorporated. All inhibitors were evaluated in an in vitro assay using purified enzyme and fluorogenic substrate peptide. One of the inhibitors showed a time-dependent inhibition, with a Ki value of 0.3 μM after 4 h incubation.
