The discovery of anthranilic acid-based MMP inhibitors. Part 1: SAR of the 3-position.
A novel series of anthranilic acid-based inhibitors of MMP-1, MMP-9, and MMP-13 was prepared and evaluated both in vitro and in vivo. The most potent compound, 6e, has in vivo activity in a rat sponge-wrapped cartilage model.
Levin
J I
JI
Wyeth-Ayerst Research, Pearl River, NY 10965, USA. levinji@war.wyeth.com
Du
M T
MT
DiJoseph
J F
JF
Killar
L M
LM
Sung
A
A
Walter
T
T
Sharr
M A
MA
Roth
C E
CE
Moy
F J
FJ
Powers
R
R
Jin
G
G
Cowling
R
R
Skotnicki
J S
JS
D000818:Animals; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D053509:Matrix Metalloproteinase 13; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013449:Sulfonamides; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat