Synthesis and separation of tritiated inhibitors of aminopeptidase A and their prodrugs
Résumé
Abstract With the aim of studying the bioavailability of two related aminopeptidase A (APA) inhibitors, we have synthesized tritiated disulfide prodrugs. These molecules, 4,4′‐dithiobis‐(3,3′‐amino)‐1,1′‐butanesulfonic acid (RB 150) and its 2,2‐dimethylpropyl ester(RB 151) bearing one tritium atom per monomer in position 2 were obtained with high purity and a final specific activity of about 30 Ci/mmol. The active radiolabeled inhibitor EC 33, Ki=270 nM for APA was obtained by reduction of the disulfide bond of RB 150. Copyright © 2004 John Wiley & Sons, Ltd.