An innovative strategy for the synthesis of a new series of potent aminopeptidase (APN or CD13) inhibitors derived from the oxepin-4-one family

Derivatives from the aminobenzosuberone family have been recently synthesized and recognized as highly selective inhibitors of aminopeptidase N (APN)/CD13 (EC 3.4.11.2), an important target for cell migration processes involved in particular in tumor invasion. We present here a much more straightforward synthesis of analogues belonging to a novel isosteric oxo series which also possesses excellent inhibitory potential against APN. Their synthesis, as reported here, relied on an interesting iodine(III)-mediated rearrangement originally described by Koser and Justik as the key step. This represents the second application of this rearrangement in medicinal chemistry.