Synthesis and structure activity relationships of novel non-peptidic metallo-aminopeptidase inhibitors.
Article Details
- CitationCopy to clipboard
Albrecht S, Defoin A, Salomon E, Tarnus C, Wetterholm A, Haeggstrom JZ
Synthesis and structure activity relationships of novel non-peptidic metallo-aminopeptidase inhibitors.
Bioorg Med Chem. 2006 Nov 1;14(21):7241-57. Epub 2006 Jul 17.
- PubMed ID
- 16844380 [ View in PubMed]
- Abstract
Racemic derivatives of 3-amino-2-tetralone were synthesised and evaluated for their ability to inhibit metallo-aminopeptidase activities. New compounds substituted in position 2 by methyl ketone, substituted oximes or hydroxamic acids as well as heterocyclic derivatives were evaluated against representative members of zinc-dependent aminopeptidases: leucine aminopeptidase (E.C. 3.4.11.1), aminopeptidase-N (E.C. 3.4.11.2), Aeromonas proteolytica aminopeptidase (E.C. 3.4.11.10), and the aminopeptidase activity of leukotriene A(4) hydrolase (E.C. 3.3.2.6). Several compounds showed K(i) values in the low micromolar range against the 'one-zinc' aminopeptidases, while most of them were rather poor inhibitors of the 'two-zinc' enzymes. This interesting selectivity profile may guide the design of new, specific inhibitors of target mammalian aminopeptidases with one active site zinc.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Ubenimex Bacterial leucyl aminopeptidase IC 50 (nM) 1.6 8 30 Details Ubenimex Leukotriene A-4 hydrolase IC 50 (nM) 500 7.5 30 Details