Aromatic sulfonyl alpha-cycloamino hydroxamic acid compounds

A compound or salt thereof, wherein:

• the compound corresponds in structure to Formula II:
• R2 is straight or branched chain aliphatic C1-C8 hydrocarbyl, C1-C6 hydrocarbyloxycarbonyl C1-C4 hydrocarbyl, aryl C1-C4 hydrocarbyl, heteroaryl C1-C4 hydrocarbyl, wherein the heteroaryl is not pyridinyl;
• aryloxy C1-C4 hydrocarbyl, or heteroaryloxy C1-C4 hydrocarbyl;
• R1 is phenyl substituted with R3 at the 4-position;
• and
• R3 is phenyl, phenoxy, or thiophenoxy, wherein the phenyl, phenoxy, or thiophenoxy is optionally substituted:
• at the meta- or para-position or both with a moiety that is selected from the group consisting of C1-C9 hydrocarbyloxy, C1-C10 hydrocarbyl, di-C1-C9 hydrocarbylamino, carboxyl C1-C8 hydrocarbyl, C1-C4 hydrocarbyloxy carbonyl C1-C4 hydrocarbyl, C1-C4 hydrocarbyloxycarbonyl C1-C4 hydrocarbyl, and carboxamido C1-C8 hydrocarbyl, or
• at the meta- and para-positions by two methyl groups or by a methylenedioxy group.

A compound or salt thereof, wherein:

• the compound corresponds in structure to Formula II:
• R2 is straight or branched chain aliphatic C1-C8 hydrocarbyl, C1-C6 hydrocarbyloxycarbonyl C1-C4 hydrocarbyl, aryl C1-C4 hydrocarbyl, heteroaryl C1-C4 hydrocarbyl, wherein the heteroaryl is not pyridinyl;
• aryloxy C1-C4 hydrocarbyl, or heteroaryloxy C1-C4 hydrocarbyl;
• R1 is phenyl substituted with R3 at the 4-position;
• and
• R3 is benzamido, nicotinamido, anilino, isonicotinamido, picolinamido, or phenylureido, wherein:
• the benzamido, nicotinamido, anilino, isonicotinamido, picolinamido, or phenylureido is optionally substituted at its own meta- or para-position or both with a moiety selected from the group consisting of nitro, C1-C8 hydrocarbyl, C1-C7 hydrocarbyloxy, amino, and amino-C2-C4 hydroxyalkyl.

A compound or salt thereof, wherein:

• the compound or salt is characterizeable in that the compound or salt selectively inhibits in vitro human MMP-13, MMP-9, and/or MMP-2 activity over in vitro human MMP-1 activity;
• the compound corresponds in structure to Formula II:
• R2 is straight or branched chain aliphatic C3-C6 hydrocarbyl, t-butoxycarbonyl, phenethyl, 2-propynyl, or 3-methoxybenzyl;
• and
• R1 is a substituent containing a 5- or 6-membered cyclohydrocarbyl, heterocyclo, aryl, or heteroaryl radical bonded directly to the depicted SO2-group, wherein:
• the cyclohydrocarbyl, heterocyclo, aryl, or heteroaryl is itself substituted at its own 4-position when a 6-membered ring or at its own 3- or 4-position when a 5-membered ring with a substituent selected from the group consisting of single-ringed cyclohydrocarbyl, single-ringed heterocyclo, single-ringed aryl, single-ringed heteroaryl, phenoxy, thiophenoxy, 4-thiopyridyl, phenylazo, phenylureido, nicotinamido, isonicotinamido, picolinamido, anilino, and benzamido.

A process for treating a pathological condition in a mammal, wherein:

• the pathological condition is treatable by inhibiting matrix metalloprotease activity;
• the process comprises administering a matrix metalloprotease inhibitor compound or a pharmaceutically acceptable salt thereof in an effective amount to the mammal;
• the compound corresponds in structure to Formula II:
• R2 is straight or branched chain aliphatic C1-C8 hydrocarbyl, C1-C6 hydrocarbyloxycarbonyl C1-C4 hydrocarbyl, aryl C1-C4 hydrocarbyl, heteroaryl C1-C4 hydrocarbyl, wherein the heteroaryl is not pyridinyl;
• aryloxy C1-C4 hydrocarbyl, or heteroaryloxy C1-C4 hydrocarbyl;
• and
• R1 is a substituent containing a 5- or 6-membered cyclohydrocarbyl, heterocyclo, aryl, or heteroaryl radical bonded directly to the depicted SO2-group, wherein:
• the cyclohydrocarbyl, heterocyclo, aryl, or heteroaryl is itself substituted at its own 4-position when a 6-membered ring or at its own 3- or 4-position when a 5-membered ring with a substituent selected from the group consisting of single-ringed cyclohydrocarbyl, single-ringed heterocyclo, single-ringed aryl, single-ringed heteroaryl, phenoxy, thiophenoxy, 4-thiopyridyl, phenylazo, phenylureido, nicotinamido, isonicotinamido, picolinamido, anilino, and benzamido.

A process for treating a pathological condition in a mammal, wherein:

• the pathological condition is treatable by inhibiting matrix metalloprotease activity;
• the process comprises administering a matrix metalloprotease inhibitor compound or a pharmaceutically acceptable salt thereof in an effective amount to the mammal;
• the compound corresponds in structure to Formula II:
• R2 is straight or branched chain aliphatic C1-C8 hydrocarbyl, C1-C6 hydrocarbyloxycarbonyl C1-C4 hydrocarbyl, aryl C1-C4 hydrocarbyl, heteroaryl C1-C4 hydrocarbyl, wherein the heteroaryl is not pyridinyl;
• aryloxy C1-C4 hydrocarbyl, or heteroaryloxy C1-C4 hydrocarbyl;
• R1 is phenyl substituted with R3 at the 4-position;
• and
• R3 is phenyl, phenoxy, or thiophenoxy, wherein the phenyl, phenoxy, or thiophenoxy is optionally substituted:
• at the meta- or para-position or both with a moiety that is selected from the group consisting of C1-C9 hydrocarbyloxy, C1-C10 hydrocarbyl, di-C1-C9 hydrocarbylamino, carboxyl C1-C8 hydrocarbyl, C1-C4 hydrocarbyloxy carbonyl C1-C4 hydrocarbyl, C1-C4 hydrocarbyloxycarbonyl C1-C4 hydrocarbyl, and carboxamido C1-C8 hydrocarbyl, or
• at the meta- and para-positions by two methyl groups or by a methylenedioxy group.

A process for treating a pathological condition in a mammal, wherein:

• the pathological condition is treatable by inhibiting matrix metalloprotease activity;
• the process comprises administering a matrix metalloprotease inhibitor compound or a pharmaceutically acceptable salt thereof in an effective amount to the mammal;
• the compound corresponds in structure to Formula II:
• R2 is straight or branched chain aliphatic C1-C8 hydrocarbyl, C1-C6 hydrocarbyloxycarbonyl C1-C4 hydrocarbyl, aryl C1-C4 hydrocarbyl, heteroaryl C1-C4 hydrocarbyl, wherein the heteroaryl is not pyridinyl;
• aryloxy C1-C4 hydrocarbyl, or heteroaryloxy C1-C4 hydrocarbyl;
• R1 is phenyl substituted with R3 at the 4-position;
• and
• R3 is benzamido, nicotinamido, anilino, isonicotinamido, picolinamido, or phenylureido, wherein:
• the benzamido, nicotinamido, anilino, isonicotinamido, picolinamido, or phenylureido is optionally substituted at its own meta- or para-position or both with a moiety selected from the group consisting of nitro, C1-C8 hydrocarbyl, C1-C7 hydrocarbyloxy, amino, and amino-C2-C4 hydroxyalkyl.

A process for treating a pathological condition in a mammal, wherein:

• the pathological condition is treatable by inhibiting matrix metalloprotease activity;
• the process comprises administering a matrix metalloprotease inhibitor compound or a pharmaceutically acceptable salt thereof in an effective amount to the mammal;
• the compound or salt is characterizeable in that the compound or salt selectively inhibits in vitro human MMP-13, MMP-9, and/or MMP-2 activity over in vitro human MMP-1 activity;
• the compound corresponds in structure to Formula II:
• R2 is straight or branched chain aliphatic C3-C6 hydrocarbyl, t-butoxycarbonyl, phenethyl, 2-propynyl, or 3-methoxybenzyl;
• and
• R1 is a substituent containing a 5- or 6-membered cyclohydrocarbyl, heterocyclo, aryl, or heteroaryl radical bonded directly to the depicted SO2-group, wherein:
• the cyclohydrocarbyl, heterocyclo, aryl, or heteroaryl is itself substituted at its own 4-position when a 6-membered ring or at its own 3- or 4-position when a 5-membered ring with a substituent selected from the group consisting of single-ringed cyclohydrocarbyl, single-ringed heterocyclo, single-ringed aryl, single-ringed heteroaryl, phenoxy, thiophenoxy, 4-thiopyridyl, phenylazo, phenylureido, nicotinamido, isonicotinamido, picolinamido, anilino, and benzamido.