P-1, P-2 '-Linked Macrocyclic Amine Derivatives As Matrix Metalloproteinase Inhibitors

A novel series of 13- and 14-membered macrocyclic amines was developed by linking the P-1, and P-2, groups. The synthesis entails stereoselective Frater alkylation to install the anti-succinate configuration and macrocyclic amination via nucleophilic displacement. This strategy resulted in a new class of conformationally constrained inhibitors that are potent ind selective for MMP-8 and 9 over MMP-1 and 3. (C) 1999 DuPont Pharmaceuticals Company. Published by Elsevier Science Ltd. All rights reserved.