813451-43-3Relevant academic research and scientific papers
Synthesis and evaluation of keto-glutamine analogues as potent inhibitors of severe acute respiratory syndrome 3CLpro
Jain, Rajendra P.,Pettersson, Hanna I.,Zhang, Jianmin,Aull, Katherine D.,Fortin, Pascal D.,Huitema, Carly,Eltis, Lindsay D.,Parrish, Jonathan C.,James, Michael N. G.,Wishart, David S.,Vederas, John C.
, p. 6113 - 6116 (2004)
The 3C-like proteinase (3CLpro) of severe acute respiratory syndrome (SARS) coronavirus is a key target for structure-based drug design against this viral infection. The enzyme recognizes peptide substrates with a glutamine residue at the P1 site. A series of keto-glutamine analogues with a phthalhydrazido group at the α-position were synthesized and tested as reversible inhibitiors against SARS 3CLpro. Attachment of tripeptide (Ac-Val-Thr-Leu) to these glutamine-based warheads generated significantly better inhibitors (4a-c, 8a-d) with IC50 values ranging from 0.60 to 70 μM.
Design, synthesis, and evaluation of inhibitors for severe acute respiratory syndrome 3C-like protease based on phthalhydrazide ketones or heteroaromatic esters
Zhang, Jianmin,Pettersson, Hanna I.,Huitema, Carly,Niu, Chunying,Yin, Jiang,James, Michael N. G.,Eltis, Lindsay D.,Vederas, John C.
, p. 1850 - 1864 (2008/02/02)
The 3C-like protease (3CLpro), which controls the severe acute respiratory syndrome (SARS) coronavirus replication, has been identified as a potential target for drug design in the treatment of SARS. A series of tetrapeptide phthalhydrazide ketones, pyridinyl esters, and their analogs have been designed, synthesized, and evaluated as potential SARS 3CLpro inhibitors. Some pyridinyl esters are identified as very potent inhibitors, with IC50 values in the nanomolar range (50-65 nM). Electrospray mass spectrometry indicates a mechanism involving acylation of the active site cysteine thiol for this class of inhibitors.
