Small-molecule inhibitor: S17092

Name

History: S17092 was described by Barelli et al. (1999) as a potent, specific and cell permeant inhibitor of human prolyl oligopeptidase.
Peptidases inhibited: Prolyl oligopeptidase (Barelli et al., 1999). K_i 1.5 nM was for a partially purified preparation of human prolyl oligopeptidase. S17092-1 did not significantly inhibit dipeptidylpeptidase IV, aminopeptidase M, aminopeptidases B, neprilysin, thimet oligopeptidase, neurolysin, calpain or angiotensin converting enzyme compound peptidase.
Mechanism: Inhibition is reversible.
Pharmaceutical relevance: S17092 has been investigated as a possible agent to increase central neuropeptide concentrations (Morain et al., 2000).

Synthesis: The synthesis was described by Portevin et al. (1996) (as compound 54).

Comment: S17092-1 is a perhydroindole carboxylic acid derivative with a C-terminal thiazolidine ring and an N-terminal 2-phenylcyclopropyl carbonyl side chain. It is one of a series of potent prolyl oligopeptidase inhibitors of the R-keto heterocyclic type that was obtained by replacing the central proline of 1-[1-(4-phenylbutanoyl)-L-prolyl]pyrrolidine with unnatural amino acids (Portevin et al., 1996). The compound has been used as a specific inhibitor of prolyl oligopeptidase in several studies exploring the biological functions of the enzyme (see Literature).