Biaryl ether retrohydroxamates as potent, long-lived, orally bioavailable MMP inhibitors.
A novel series of biaryl ether reverse hydroxamate MMP inhibitors has been developed. These compounds are potent MMP-2 inhibitors with limited activity against MMP-1. Select members of this series exhibit excellent pharmacokinetic properties with long elimination half-lives (7 h) and high oral bioavailability (100%).
Michaelides
M R
MR
Cancer Research Area, Abbott Laboratories, Dept. 47J, Bldg. AP10, 100 Abbott Park Road, Abbott Park, IL 60064, USA. michael.michaelides@abbott.com
Dellaria
J F
JF
Gong
J
J
Holms
J H
JH
Bouska
J J
JJ
Stacey
J
J
Wada
C K
CK
Heyman
H R
HR
Curtin
M L
ML
Guo
Y
Y
Goodfellow
C L
CL
Elmore
I B
IB
Albert
D H
DH
Magoc
T J
TJ
Marcotte
P A
PA
Morgan
D W
DW
Davidsen
S K
SK
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics; D001682:Biological Availability; D004791:Enzyme Inhibitors / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics; D006207:Half-Life; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D061965:Matrix Metalloproteinase Inhibitors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors