Aromatic sulfonyl alpha-hydroxy hydroxamic acid compounds

A compound corresponding to Formula I:

• 1139
• wherein
• R2 is hydrido, C1-C4 hydrocarbyl, hydroxy-C1-C4 hydrocarbyl, C1-C4 hydrocarbyloxy, halo-C1-C4 hydrocarbyl, C1-C4 hydrocarbylc)xymethyl, aminomethyl, (N-C1-C3 hydrocarbyl) aminomethyl, (N1 N-di-C1-C3 hydrocarbyl)aminomethyl, (N-morpholino)methyl, (N-pyrrolidino)methyl, or (N-thiomorpholino)methyl;
• and
• R1 is a substituent containing a 5- or 6-membered cyclohydrocarbyl, heterocyclo, aryl or heteroaryl radical bonded directly to the depicted SO2-group that is itself substituted at its own 4-position when a 6-membered ring and at its own 3- or 4-position when a 5-membered ring with a substituent R3 selected from the group consisting of one other single-ringed cyclohydrocarbyl, heterocyclo, aryl or heteroaryl group, a C3-C14 hydrocarbyl group, a C2-C14 hydrocarbyloxy group, a phenoxy group, a thiophenoxy group, a 4-thiopyridyl group, a phenylazo group, a ureidophenyl group, a nicotinamido group, an isonicotinamido group, a picolinamido group, an anilino group and a benzamido group.

A compound corresponding to Formula II:

• 1140
• wherein
• R2 is hydrido, C1-C4 hydrocarbyl, hydroxy-C1-C4 hydrocarbyl, C1-C4 hydrocarbyloxy, halo-C1-C4 hydrocarbyl, C1-C4 hydrocarbyloxymethyl, aminomethyl, (N-C1-C3 hydrocarbyl)aminomethyl, (N,N-di-C1-C3 hydrocarbyl)aminomethyl, (N-morpholino)methyl, (N-pyrrolidino)methyl, or (N-thiomorpholino)methyl;
• and
• Ph is phenyl substituted with R3 at the 4-position, and R3 is a phenyl, phenoxy, thiophenoxy, anilino, phenylazo, benzamido, nicotinamido, isonicotinamido, picolinamido or ureidophenyl group, and said PhR3 group has a length greater than about that of a octyl group and less than about that of a stearyl group, and when rotated about an axis drawn through the SO2-bonded 1-position and the 4-position of said phenyl ring, Ph, defines a three-dimensional volume whose widest dimension in a direction transverse to the axis of rotation is about that of one furanyl ring to about that of two phenyl rings.

A process for treating a host mammal having a condition associated with pathological matrix metalloprotease activity that comprises administering a compound corresponding in structure to Formula I in an MMP enzyme-inhibiting effective amount to a mammalian host having such a condition:

• 1152
• wherein
• R2 is hydrido, C1-C4 hydrocarbyl, hydroxy-C1-C4 hydrocarbyl, C1-C4 hydrocarbyloxy, halo-C1-C4 hydrocarbyl, C1-C4 hydrocarbyloxymethyl, aminomethyl, (N-C1-C3 hydrocarbyl)aminomethyl, (N,N-di-C1-C3 hydrocarbyl) aminomethyl, (N-morpholino) methyl, (N-pyrrolidino)methyl, or (N-thiomorpholino)methyl;
• and
• R1 is a substituent containing a 5- or 6-membered cyclohydrocarbyl, heterocyclo, aryl or heteroaryl radical bonded directly to the depicted SO2-group and having a length greater than about that of a hexyl group and less than about that of an eicosyl group, said R1 defining a three-dimensional volume, when rotated about an axis drawn through the SO2-bonded 1-position and the 4-position of a 6-membered ring radical or drawn through the SO2-bonded 1-position and the center of 3,4-bond of a 5-membered ring radical, whose widest dimension in a direction transverse to the axis of rotation is about that of one furanyl ring to about that of two phenyl rings.