Orally bioavailable dual MMP-1/MMP-14 sparing, MMP-13 selective alpha-sulfone hydroxamates.
A series of phenyl piperidine alpha-sulfone hydroxamate derivatives has been prepared utilizing a combination of solution-phase and resin-bound library technologies to afford compounds that are potent and highly selective for MMP-13, are dual-sparing of MMP-1 and MMP-14 (MT1-MMP) and exhibit oral bioavailability in rats.
Kolodziej
Stephen A
SA
Department of Medicinal Chemistry, Pfizer Research & Development, St. Louis, MO 63198, USA.
Hockerman
Susan L
SL
Boehm
Terri L
TL
Carroll
Jeffery N
JN
DeCrescenzo
Gary A
GA
McDonald
Joseph J
JJ
Mischke
Debbie A
DA
Munie
Grace E
GE
Fletcher
Theresa R
TR
Rico
Joseph G
JG
Stehle
Nathan W
NW
Swearingen
Craig
C
Becker
Daniel P
DP
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D006877:Hydroxamic Acids / Q000008:administration & dosage; D020781:Matrix Metalloproteinase 1 / Q000187:drug effects; D053511:Matrix Metalloproteinase 14 / Q000187:drug effects; D061965:Matrix Metalloproteinase Inhibitors; D010880:Piperidines; D051381:Rats; D054852:Small Molecule Libraries; D012995:Solubility; D013379:Substrate Specificity; D013450:Sulfones
D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D010880:Piperidines; D054852:Small Molecule Libraries; D013450:Sulfones; D020781:Matrix Metalloproteinase 1; D053511:Matrix Metalloproteinase 14