211186-22-0Relevant academic research and scientific papers
COMPOUNDS, COMPOSITIONS AND METHODS FOR STABILIZING TRANSTHYRETIN AND INHIBITING TRANSTHYRETIN MISFOLDING
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, (2021/08/06)
Provided herein are compounds having activity against TTR related conditions, and pharmaceutically accepted salts and solvates thereof. Also provided are methods of using the compounds for inhibiting and preventing TTR aggregation and/or amyloid formation in the peripheral nerves, kidney, cardiac tissue, eye and CNS, and of treating a subject with peripheral TTR amyloidosis.
Viral polymerase inhibitors
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, (2008/06/13)
A compound of the formula I: wherein: X is CH or N; Y is O or S; Z is OH, NH2, NMeR3, NHR3; OR3 or 5- or 6-membered heterocycle, having 1 to 4 heteroatoms selected from 0, N and S, said heterocycle being optionally substituted with from 1 to 4 substituents; A is N, COR7 or CR5, wherein R5 is H, halogen, or (C1-6) alkyl and R7 is H or (C1-6 alkyl), with the proviso that X and A are not both N; R6 is H, halogen, (C1-6 alkyl) or OR7, wherein R7 is H or (C1-6 alkyl); R1 is selected from the group consisting of 5- or 6-membered heterocycle having 1 to 4 heteroatoms selected from O, N, and S, phenyl, phenyl(C1-3)alkyl, (C2-6)alkenyl, phenyl(C2-6)alkenyl, (C3-6)cycloalkyl, (C1-6)alkyl, CF3, 9- or 10-membered heterobicycle having 1 to 4 heteroatoms selected from O, N and S, wherein said heterocycle, phenyl, phenyl(C2-6)alkenyl and phenyl(C1-3)alkyl), alkenyl, cycloalkyl, (C1-6)alkyl, and heterobicycle are all optionally substituted with from 1 to 4 substituents R2 is selected from (C1-6)alkyl, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C1-3)alkyl, (C6-10)bicycloalkyl, adamantyl, phenyl, and pyridyl, all of which is optionally substituted with from1 to 4 substituents; R3 is selected from H, (C1-6)alkyl, (C3-6)cycloalkyl, (C36)cycloalkyl(C1-6)alkyl, (C6-10)aryl, (C6-10)aryl(C1-6)alkyl, (C2-6)alkenyl, (C3-6)cycloalkyl(C2-6)alkenyl, (C6-10)aryl(C2-6)alkenyl, N{(C1-6)alkyl}2, NHCOO(C1-6)alkyl(C6-10)aryl, NHCO(C6-10)aryl, (C1-6)alkyl-5- or 10-atom heterocycle, having 1 to 4 heteroatoms selected from O, N and S, and 5- or 10-atom heterocycle having 1 to 4 heteroatoms selected from O, N and S; wherein said alkyl, cycloalkyl, aryl, alkenyl and heterocycle are all optionally substituted with from 1 to 4 substituents; n is zero or 1; or a detectable derivative or salt thereof. The compounds of the invention may be used as inhibitors of hepatitis C virus replication. The invention further provides a method for treating or preventing hepatitis C virus infection.
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.
