Small-molecule inhibitor: SSR69071

Name

History: SSR69071 was described by Varga et al. (2003) (Sanofi-Synthelabo Research).
Peptidases inhibited: Inhibits human neutrophil elastase.
Mechanism: SSR69071 is described as a competitive, slow tight-binding inhibitor of neutrophil elastase (Varga et al., 2003). The values for K_i and k_on are given as 16.8 pM and 0.183 x 10⁶ Ms^-1, respectively (Kapui et al., 2003).
Pharmaceutical relevance: The activity of neutrophil elastase evidently contributes to a variety of disease processes, including pulmonary emphysema, adult respiratory disease syndrome and chronic obstructuve pulmonary disease (Varga et al., 2003). Because of this, inhibitors of the enzyme have therapeutic potential.

Structure
Chemical/biochemical name: 2-[(4-isopropyl-6-methoxy-1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methoxy]-9- (2-piperidin-1-ylethoxy)-4H-pyrido[1,2-a]pyrimidin-4-one

Comment: SSR69071 is a saccharin-type, mechanism-based inhibitor that is orally-active.
Reviews: Saccharins as serine peptidase inhibitors have been reviewed by Powers et al. (2002), pp. 4725-4728.