Small-molecule inhibitor: rupintrivir

Name

History: The history of the discovery of AG7088/Rupintrivir by workers at Agouron/Pfizer (e.g. Patick et al., 1999) has been reviewed by Powers et al. (2002).
Peptidases inhibited: Inhibits the human rhinovirus picornain 3C (Binford et al., 2005). Inactive against the 3C-like peptidase of SARS coronavirus (Shie et al., 2005).
Mechanism: Inhibition is irreversible.
Pharmaceutical relevance: Under consideration as a drug against rhinovirus infection (Hayden et al., 2003).

CID at PubChem: 154226
ChEBI: 124969
Structure
Chemical/biochemical name: 4-[2-[(4-fluorophenyl)methyl]-6-methyl-5-(5-methyloxazol-3-yl)carbonylamino-4- oxo-heptanoyl]amino-5-(2-oxopyrrolidin-3-yl)-pent-2-enoate
Formula weight: 599

Inhibitor class: This compound belongs to the class of Michael acceptor inhibitors. These are irreversible inhibitors specific for cysteine and threonine peptidases. The class includes vinyl sulfones and alpha, beta-unsaturated derivatives of amino acids and peptides. These inhibitors act by forming covalent bonds to the active site thiol of a cysteine peptidase. They have negligible reactivity with small-molecule thiol compounds and serine peptidases. The reaction proceeds via a Michael addition, with an attack on the beta-carbon of the inhibitor by the active site cysteine residue, followed by protonation of the alpha-carbon to form the thioether derivative. Reviewed by Powers et al. (2002), pp. 4683 - 4694.
Reviews: Binford et al. (2005); Powers et al. (2002)