Figure 2.

Selection of HNE inhibitors that have reached clinical development. a) Biologicals such as elafin^[11] were the first class of HNE-inhibiting drugs. These compounds are only suitable for i.v. application. b) As a second prominent class, covalent drugs that acylate serine in the active site of the enzyme, such as sivelestat (1), or transition-state mimetics, such as freselestat (2), were described. A tremendous effort was required to find the first reversible and selective small-molecule drugs as a third class. A prominent example is alvelestat (3).