The discovery of anthranilic acid-based MMP inhibitors. Part 2: SAR of the 5-position and P1(1) groups.
A novel series of anthranilic acid-based inhibitors of MMP-1, MMP-9, MMP-13, and TACE was prepared and evaluated. Selective inhibitors of MMP-9, MMP-13, and TACE were identified, including the potent, orally active MMP-13 inhibitor 4p.
Levin
J I
JI
Wyeth-Ayerst Research, 401 N. Middletown Rd., Pearl River, NY 10965, USA. levinji@war.wyeth.com
Chen
J
J
Du
M
M
Hogan
M
M
Kincaid
S
S
Nelson
F C
FC
Venkatesan
A M
AM
Wehr
T
T
Zask
A
A
DiJoseph
J
J
Killar
L M
LM
Skala
S
S
Sung
A
A
Sharr
M
M
Roth
C
C
Jin
G
G
Cowling
R
R
Mohler
K M
KM
Black
R A
RA
March
C J
CJ
Skotnicki
J S
JS
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D017364:Collagenases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D062367:ortho-Aminobenzoates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D062367:ortho-Aminobenzoates; D051722:ADAM Proteins; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9; D000072198:ADAM17 Protein