Amino-benzosuberone: A novel warhead for selective inhibition of human aminopeptidase-N/CD13

Racemic aminoindanone 2, amino benzosuberones 3, 4, and aminocycloheptanone 5 were synthesised and evaluated as inhibitors of four representative members of zinc-dependent aminopeptidases. Ki values in the low micromolar range against ‘one zinc’ aminopeptidases are obtained. The stability of these compounds was studied. This paper describes the design and synthesis of compounds belonging to a novel class of highly selective mammalian CD13 inhibitors. Racemic homologues of 3-amino-2-tetralone 1 were synthesised and evaluated for their ability to selectively inhibit the membrane-bound, zinc-dependent aminopeptidase-N/CD13 (EC 3.4.11.2). Some of these novel non-peptidic compounds are potent, competitive inhibitors of the mammalian enzyme, with Ki values in the low micromolar range in spite of their minimal size (MW