Design and synthesis of 2-oxo-imidazolidine-4-carboxylic acid hydroxyamides as potent matrix metalloproteinase-13 inhibitors.
A novel series of imidazolidinone-based matrix metalloproteinase (MMP) inhibitors was discovered by structural modification of pyrrolidinone la. Potent inhibition of MMP-13 was exhibited by the analogues having 4-(4-fluorophenoxy)phenyl (4a, IC50 = 3 nM) and 4-(naphth-2-yloxy)phenyl (4h, IC50 = 4 nM) as P1' groups.
Robinson
R P
RP
Pfizer Global Research & Development, Groton Laboratories, CT 06340, USA. ralph_p_robinson@groton.pfizer.com
Laird
E R
ER
Donahue
K M
KM
Lopresti-Morrow
L L
LL
Mitchell
P G
PG
Reese
M R
MR
Reeves
L M
LM
Rouch
A I
AI
Stam
E J
EJ
Yocum
S A
SA
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D053509:Matrix Metalloproteinase 13; D061965:Matrix Metalloproteinase Inhibitors; D013237:Stereoisomerism
D000577:Amides; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D007093:Imidazoles; D061965:Matrix Metalloproteinase Inhibitors; D053509:Matrix Metalloproteinase 13