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P1, P2'-linked macrocyclic amine derivatives as matrix metalloproteinase inhibitors
1DuPont Pharmaceuticals Company, Department of Chemical and Physical Sciences, Wilmington, Delaware 19880-0500, USA.
Bioorganic & Medicinal Chemistry Letters
|June 9, 1999
Abstract:
A novel series of 13- and 14-membered macrocyclic amines was developed by linking the P1 and P2' 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 and selective for MMP-8 and 9 over MMP-1 and 3.

