title: P1, P2'-linked macrocyclic amine derivatives as matrix metalloproteinase inhibitors.
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.
authors.affiliation: DuPont Pharmaceuticals Company, Department of Chemical and Physical Sciences, Wilmington, Delaware 19880-0500, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Duan
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: C B
authors.initials: CB
authors.lastname: Xue
authors.forename: Z R
authors.initials: ZR
authors.lastname: Wasserman
authors.forename: K D
authors.initials: KD
authors.lastname: Hardman
authors.forename: M B
authors.initials: MB
authors.lastname: Covington
authors.forename: R R
authors.initials: RR
authors.lastname: Copeland
authors.forename: E C
authors.initials: EC
authors.lastname: Arner
authors.forename: C P
authors.initials: CP
authors.lastname: Decicco
mesh_terms: D000588:Amines / Q000737:chemistry / Q000494:pharmacology*; D003198:Computer Simulation; D005109:Extracellular Matrix / Q000201:enzymology*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000588:Amines; D011480:Protease Inhibitors; D008666:Metalloendopeptidases