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Articles 1 - 5 of 5
Full-Text Articles in Physical Sciences and Mathematics
Mmp-13 Selective Α-Sulfone Hydroxamates: A Survey Of P1' Heterocyclic Amide Isosteres, Thomas E. Barta, Daniel P. Becker, Louis J. Bedell, Alan M. Easton
Mmp-13 Selective Α-Sulfone Hydroxamates: A Survey Of P1' Heterocyclic Amide Isosteres, Thomas E. Barta, Daniel P. Becker, Louis J. Bedell, Alan M. Easton
Chemistry: Faculty Publications and Other Works
Seeking compounds preferentially potent and selective for MMP-13, we reported in the preceding Letter on a series of hydroxamic acids with a flexible benzamide tail groups.(1a) Here, we replace the amide moiety with non-hydrolyzable heterocycles in an effort to improve half-life. We identify a hydroxamate tetrazole 4e that spares MMP-1 and -14, shows >400-fold selectivity versus MMP-8 and >600-fold selectivity versus MMP-2, and has a 4.8 h half-life in rats. X-ray data (1.9 Å) for tetrazole 4c is presented.
Mmp-13 Selective Alpha-Sulfone Hydroxamates: Identification Of Selective P1' Amides, Yvette M. Fobian, John N. Freskos, Thomas E. Barta, Louis J. Bedell, Daniel Becker
Mmp-13 Selective Alpha-Sulfone Hydroxamates: Identification Of Selective P1' Amides, Yvette M. Fobian, John N. Freskos, Thomas E. Barta, Louis J. Bedell, Daniel Becker
Chemistry: Faculty Publications and Other Works
Continuing our interest in designing compounds preferentially potent and selective for MMP-13, we report on a series of hydroxamic acids with a flexible amide P1' substituents. We identify an amide which spares both MMP-1 and -14, and shows >500 fold selectivity for MMP-13 versus MMP-2 and -8.
Mmp-13 Selective Isonipecotamide Alpha-Sulfone Hydroxamates, Stephen A. Kolodziej, Susan L. Hockerman, Gary A. Decrescenzo, Joseph J. Mcdonald, Grace E. Munie, Theresa R. Fletcher, Nathan Stehle, Craig Swearingen, Daniel Becker
Mmp-13 Selective Isonipecotamide Alpha-Sulfone Hydroxamates, Stephen A. Kolodziej, Susan L. Hockerman, Gary A. Decrescenzo, Joseph J. Mcdonald, Grace E. Munie, Theresa R. Fletcher, Nathan Stehle, Craig Swearingen, Daniel Becker
Chemistry: Faculty Publications and Other Works
A series of N-aryl isonipecotamide α-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.
Orally Bioavailable Dual Mmp-1/Mmp-14 Sparing, Mmp-13 Selective Alpha-Sulfone Hydroxamates, Daniel Becker, Stephen A. Kolodziej, Susan L. Hockerman, Terri L. Boehm, Jeffery N. Carroll
Orally Bioavailable Dual Mmp-1/Mmp-14 Sparing, Mmp-13 Selective Alpha-Sulfone Hydroxamates, Daniel Becker, Stephen A. Kolodziej, Susan L. Hockerman, Terri L. Boehm, Jeffery N. Carroll
Chemistry: Faculty Publications and Other Works
A series of phenyl piperidine α-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.
Alpha-Alkyl-Alpha-Amino-Beta-Sulphone Hydroxamates As Potent Mmp Inhibitors That Spare Mmp-1, Daniel Becker, Gary A. Decrescenzo, John Freskos, Daniel P. Getman
Alpha-Alkyl-Alpha-Amino-Beta-Sulphone Hydroxamates As Potent Mmp Inhibitors That Spare Mmp-1, Daniel Becker, Gary A. Decrescenzo, John Freskos, Daniel P. Getman
Chemistry: Faculty Publications and Other Works
A series of α-alkyl-α-amino-β-sulphone hydroxamates was prepared and evaluated for potency versus MMP-2 and MMP-13, and for selectivity versus MMP-1. Low nanomolar potency was obtained with selectivity versus MMP-1 ranging from >10 to >1000. Selected compounds were orally bioavailable.