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

doi:10.1016/j.bmcl.2011.03.099

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

Department of Chemistry and Biochemistry

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	American English
Journal	Chemistry: Faculty Publications and Other Works
Volume	21
Issue number	10
DOIs	https://doi.org/10.1016/j.bmcl.2011.03.099
State	Published - May 15 2011

Keywords

MMP-13
hydroxamates

Disciplines

Chemistry

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title = "MMP-13 Selective α-sulfone Hydroxamates: a Survey of P1' Heterocyclic Amide Isosteres",

abstract = " 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 {\AA}) for tetrazole 4c is presented.",

keywords = "MMP-13, hydroxamates",

author = "Barta, {Thomas E.} and Becker, {Daniel P.} and Bedell, {Louis J.} and Easton, {Alan M.}",

year = "2011",

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T1 - MMP-13 Selective α-sulfone Hydroxamates: a Survey of P1' Heterocyclic Amide Isosteres

AU - Barta, Thomas E.

AU - Becker, Daniel P.

AU - Bedell, Louis J.

AU - Easton, Alan M.

PY - 2011/5/15

Y1 - 2011/5/15

N2 - 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.

AB - 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.

KW - MMP-13

KW - hydroxamates

UR - https://ecommons.luc.edu/chemistry_facpubs/35

U2 - 10.1016/j.bmcl.2011.03.099

DO - 10.1016/j.bmcl.2011.03.099

M3 - Article

VL - 21

JO - Chemistry: Faculty Publications and Other Works

JF - Chemistry: Faculty Publications and Other Works

IS - 10

ER -

MMP-13 Selective α-sulfone Hydroxamates: a Survey of P1' Heterocyclic Amide Isosteres

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