Diacylaminomethyl ketone

Additional cycles of SBDD were imdertaken. They focused on separately optimizing each of the two halves of the symmetric diacylaminomethyl ketone inhibitor (Desjarlais et al., 1998 Thompson et al.. 

Figure 17.3 Schematic representation of the design of the symmetric cathepsin K inhibitor diacylaminomethyl ketone (1,3-bis[[A/-[(phenylmethoxy)carbonyl]-L-leucyl]amino]-2-propanone), based on the crystal structures of papain bound to leupeptin (Leu-Leu-Arg-aldehyde) and to Cbz-Leu-Leu-Leu-aldehyde, and an example of its further optimization.

---