The discovery of anthranilic acid-based MMP inhibitors. Part 3: incorporation of basic amines.
Anthranilic acid derivatives bearing basic amines were prepared and evaluated in vitro and in vivo as inhibitors of MMP-1, MMP-9, MMP-13, and TACE. Piperazine 4u has been identified as a potent, selective, orally active inhibitor of MMP-9 and MMP-13.
Levin
J I
JI
Wyeth-Ayerst Research, 401N. Middletown Rd., Pearl River, NY 10965, USA. levinji@war.wyeth.com
Chen
J M
JM
Du
M T
MT
Nelson
F C
FC
Wehr
T
T
DiJoseph
J F
JF
Killar
L M
LM
Skala
S
S
Sung
A
A
Sharr
M A
MA
Roth
C E
CE
Jin
G
G
Cowling
R
R
Di
L
L
Sherman
M
M
Xu
Z B
ZB
March
C J
CJ
Mohler
K M
KM
Black
R A
RA
Skotnicki
J S
JS
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000588:Amines / Q000737:chemistry*; D000818:Animals; D001665:Binding Sites; D017364:Collagenases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000737:chemistry; D007375:Interleukin-1; D053583:Interleukin-1beta; D009682:Magnetic Resonance Spectroscopy; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases; D051379:Mice; D008958:Models, Molecular; D010003:Osteoarthritis / Q000188:drug therapy; D051381:Rats; D013329:Structure-Activity Relationship; D062367:ortho-Aminobenzoates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000588:Amines; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D007375:Interleukin-1; D053583:Interleukin-1beta; D061965:Matrix Metalloproteinase Inhibitors; D062367:ortho-Aminobenzoates; D051722:ADAM Proteins; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D008666:Metalloendopeptidases; C507081:Mmp13 protein, mouse; C507083:Mmp13 protein, rat; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D000072198:ADAM17 Protein; C000606463:Adam17 protein, mouse; C000606464:Adam17 protein, rat