P1, P2'-linked macrocyclic amine derivatives as matrix metalloproteinase inhibitors.
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.
Duan
J J
JJ
DuPont Pharmaceuticals Company, Department of Chemical and Physical Sciences, Wilmington, Delaware 19880-0500, USA.
Chen
L
L
Xue
C B
CB
Wasserman
Z R
ZR
Hardman
K D
KD
Covington
M B
MB
Copeland
R R
RR
Arner
E C
EC
Decicco
C P
CP
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*
D000588:Amines; D011480:Protease Inhibitors; D008666:Metalloendopeptidases