We performed a series of systematic structure–activity relationship (SAR) studies on 2 , exploring the 4- and 5-positions of the central oxazole, the C2 acyl side chain, and the central heterocyclic ring, and found that each independently affects the potency or selectivity of the inhibitor, Figure 2 .

Synthesis of oxazole-based inhibitors bearing a C5 aryl substituent and containing additional conformational constraints in the C2 acyl side chain.

The synthesis of candidate inhibitors that bear a nonaro-matic oxazole C5-substituent.

Stille coupling with 2-bromopyridine produced the C5-substituted oxazoles, which were converted to the corresponding ketones by TBS ether deprotection (Bu4NF) and oxidation of the liberated alcohols using Dess-Martin Periodinane.

Oxazole Fragment Synthesis