α-Amino-β-sulphone hydroxamates as potent MMP-13 inhibitors that spare MMP-1

Daniel P Becker; Thomas E Barta; Louis Bedell; Gary DeCrescenzo; John Freskos; Daniel P Getman; Susan L Hockerman; Madeleine Li; Pramod Mehta; Brent Mischke; Grace E Munie; Craig Swearingen; Clara I Villamil

doi:10.1016/S0960-894X(01)00556-X

α-Amino-β-sulphone hydroxamates as potent MMP-13 inhibitors that spare MMP-1

Daniel P Becker, Thomas E Barta, Louis Bedell, Gary DeCrescenzo, John Freskos, Daniel P Getman, Susan L Hockerman, Madeleine Li, Pramod Mehta, Brent Mischke, Grace E Munie, Craig Swearingen, Clara I Villamil

Department of Chemistry and Biochemistry

Pharmacia Research & Development

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

Abstract

A series of α-amino-β-sulphone hydroxamates was prepared and evaluated for potency versus MMP-13 and selectivity versus MMP-1. Various substituents were employed on the α-amino group (P1 position), as well as different groups attached to the sulphone group extending into P1′. Low nanomolar potency was obtained for MMP-13 with selectivity versus MMP-1 of >1000× for a number of analogues.

α-Amino-β-sulphone hydroxamates were prepared, which are potent MMP-13 inhibitors with selectivity versus MMP-1 of >1000× for a number of analogues. Selected compounds exhibited oral bioavailability.

Original language	American English
Journal	Chemistry: Faculty Publications and Other Works
Volume	11
Issue number	20
DOIs	https://doi.org/10.1016/S0960-894X(01)00556-X
State	Published - Oct 1 2001

Keywords

MMP-13 inhibitors
MMP-1 inhibitors
oral bioavailability

Disciplines

Chemistry

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-Amino- -sulphone hydroxamates as potent MMP-13 inhibitors thatFinal published version, 287 KBLicense: Unspecified

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Becker, D. P., Barta, T. E., Bedell, L., DeCrescenzo, G., Freskos, J., Getman, D. P., Hockerman, S. L., Li, M., Mehta, P., Mischke, B., Munie, G. E., Swearingen, C., & Villamil, C. I. (2001). α-Amino-β-sulphone hydroxamates as potent MMP-13 inhibitors that spare MMP-1. Chemistry: Faculty Publications and Other Works, 11(20). https://doi.org/10.1016/S0960-894X(01)00556-X

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abstract = " A series of α-amino-β-sulphone hydroxamates was prepared and evaluated for potency versus MMP-13 and selectivity versus MMP-1. Various substituents were employed on the α-amino group (P1 position), as well as different groups attached to the sulphone group extending into P1′. Low nanomolar potency was obtained for MMP-13 with selectivity versus MMP-1 of >1000× for a number of analogues. α-Amino-β-sulphone hydroxamates were prepared, which are potent MMP-13 inhibitors with selectivity versus MMP-1 of >1000× for a number of analogues. Selected compounds exhibited oral bioavailability.",

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T1 - α-Amino-β-sulphone hydroxamates as potent MMP-13 inhibitors that spare MMP-1

AU - Becker, Daniel P

AU - Barta, Thomas E

AU - Bedell, Louis

AU - DeCrescenzo, Gary

AU - Freskos, John

AU - Getman, Daniel P

AU - Hockerman, Susan L

AU - Li, Madeleine

AU - Mehta, Pramod

AU - Mischke, Brent

AU - Munie, Grace E

AU - Swearingen, Craig

AU - Villamil, Clara I

PY - 2001/10/1

Y1 - 2001/10/1

N2 - A series of α-amino-β-sulphone hydroxamates was prepared and evaluated for potency versus MMP-13 and selectivity versus MMP-1. Various substituents were employed on the α-amino group (P1 position), as well as different groups attached to the sulphone group extending into P1′. Low nanomolar potency was obtained for MMP-13 with selectivity versus MMP-1 of >1000× for a number of analogues. α-Amino-β-sulphone hydroxamates were prepared, which are potent MMP-13 inhibitors with selectivity versus MMP-1 of >1000× for a number of analogues. Selected compounds exhibited oral bioavailability.

AB - A series of α-amino-β-sulphone hydroxamates was prepared and evaluated for potency versus MMP-13 and selectivity versus MMP-1. Various substituents were employed on the α-amino group (P1 position), as well as different groups attached to the sulphone group extending into P1′. Low nanomolar potency was obtained for MMP-13 with selectivity versus MMP-1 of >1000× for a number of analogues. α-Amino-β-sulphone hydroxamates were prepared, which are potent MMP-13 inhibitors with selectivity versus MMP-1 of >1000× for a number of analogues. Selected compounds exhibited oral bioavailability.

KW - MMP-13 inhibitors

KW - MMP-1 inhibitors

KW - oral bioavailability

UR - https://ecommons.luc.edu/chemistry_facpubs/112

U2 - 10.1016/S0960-894X(01)00556-X

DO - 10.1016/S0960-894X(01)00556-X

M3 - Article

VL - 11

JO - Chemistry: Faculty Publications and Other Works

JF - Chemistry: Faculty Publications and Other Works

IS - 20

ER -

α-Amino-β-sulphone hydroxamates as potent MMP-13 inhibitors that spare MMP-1

Abstract

Keywords

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