343566-87-0Relevant academic research and scientific papers
Antipicornaviral compounds and compositions, their pharmaceutical uses, and materials for their synthesis
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, (2008/06/13)
Compounds of the formula: where the formula variables are as defined herein, are disclosed that advantageously inhibit or block the biological activity of the picornaviral 3C protease. Also disclosed are compounds of the formula: where the formula variables are as defined herein that advantageously inhibit or block the biological activity of the picornaviral 3C protease. These compounds, as well as pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with one or more picornaviruses, such as rhinovirus 3C proteases. Intermediates and synthetic methods for preparing such compounds are also described.
Structure-based design of irreversible, tripeptidyl human rhinovirus 3C protease inhibitors containing N-methyl amino acids
Dragovich, Peter S.,Webber, Stephen E.,Prins, Thomas J.,Zhou, Ru,Marakovits, Joseph T.,Tikhe, Jayashree G.,Fuhrman, Shella A.,Patick, Amy K.,Matthews, David A.,Ford, Clifford E.,Brown, Edward L.,Binford, Susan L.,Meador III, James W.,Ferre, Rose Ann,Worland, Stephen T.
, p. 2189 - 2194 (2007/10/03)
Tripeptide-derived molecules incorporating N-methyl amino acid residues and C-terminal Michael acceptor moieties were evaluated as irreversible inhibitors of the cysteine-containing human rhinovirus 3C protease (3CP). Such compounds displayed good 3CP inh
Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 2. Peptide structure- activity studies
Dragovich, Peter S.,Webber, Stephen E.,Babine, Robert E.,Fuhrman, Sheila A.,Patick, Amy K.,Matthews, David A.,Reich, Siegfried H.,Marakovits, Joseph T.,Prins, Thomas J.,Zhou, Ru,Tikhe, Jayashree,Littlefield, Ethel S.,Bleckman, Ted M.,Wallace, Michael B.,Little, Thomas L.,Ford, Clifford E.,Meador III, James W.,Ferre, Rose Ann,Brown, Edward L.,Binford, Susan L.,DeLisle, Dorothy M.,Worland, Stephen T.
, p. 2819 - 2834 (2007/10/03)
The structure-based design, chemical synthesis, and biological evaluation of various peptidederived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds are comprised of an ethyl propenoate Michael acceptor moiety and a tripeptidyl binding determinant. The systematic modification of each amino acid residue present in the binding determinant as well as the N-terminal functionality is described. Such modifications are shown to provide irreversible HRV-14 3CP inhibitors with anti-3CP activities (k(obs)/[I]) ranging from 60 to 280 000 M-1 s-1 and antiviral EC50's which approach 0.15 μM. An optimized inhibitor which incorporates several improvements identified by the structure-activity studies is also described. This molecule displays very rapid irreversible inhibition of HRV-14 3CP (k(obs)/[I] = 800 000 M-1 s-1) and potent antiviral activity against HRV-14 in cell culture (EC50 = 0.056 μM). A 1.9 A? crystal structure of an S-alkylthiocarbamate-containing inhibitor complexed with HRV-2 3CP is also detailed.
Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 1. Michael acceptor structre-activity studies
Dragovich, Peter S.,Webber, Stephen E.,Babine, Robert E.,Fuhrman, Shella A.,Patick, Amy K.,Matthews, David A.,Lee, Caroline A.,Reich, Siegfried H.,Prins, Thomas J.,Marakovits, Joseph T.,Littlefield, Ethel S.,Zhou, Ru,Tikhe, Jayashree,Ford, Clifford E.,Wallace, Michael B.,Meador III, James W.,Ferre, Rose Ann,Brown, Edward L.,Binford, Susan L.,Harr, James E. V.,DeLisle, Dorothy M.,Worland, Stephen T.
, p. 2806 - 2818 (2007/10/03)
The structure-based design, chemical synthesis, and biological evaluation of peptide-derived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds incorporate various Michael acceptor moieties and are shown to irreversibly bin
