Sulfonyl aryl or heteroaryl hydroxamic acid compounds

Abstract

A sulfonyl aromatic or heteroaromatic ring hydroxamic acid compound that inter alia inhibits matrix metalloprotease activity is disclosed as are a treatment process that comprises administering a contemplated sulfonyl aromatic or heteroaromatic ring hydroxamic acid compound in a MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity.

1 . A compound or a pharmaceutically acceptable salt thereof, wherein: 
 the compound corresponds in structure to Formula A:                          y and z are each zero or one;    the sum of z+y is zero or one;    the ring structure W is selected from the group consisting of phenyl, pyridinyl, and thienyl;    X is selected from the group consisting of —CH 2 — and —NR 9 —;    R 9  is selected from the group consisting of hydrogen, aryl, alkyl, and arylalkyl;    R 1  is selected from the group consisting of piperidinyl, piperazinyl, and pyrrolidinyl, wherein: 
 the piperidinyl, piperazinyl, and pyrrolidinyl comprise a nitrogen ring atom bonded directly to the depicted SO 2 -group, and  
 the piperidinyl, piperazinyl, and pyrrolidinyl are substituted with a phenyl-containing substituent;  
   R 1  has a length greater than about that of a hexyl group and less than about that of an eicosyl group;    R 1  defines a three-dimensional volume, when rotated about an axis drawn through the SO 2 -bonded 1-position and the 4-position of the piperidinyl or piperazinyl or drawn through the SO 2 -bonded 1-position and the center of 3,4-bond of pyrrolidinyl, 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;    as to R 2  and R 3 : 
 R 2  and R 3  are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, R a oxyalkyl, hydroxyl, thiol, R a thioalkyl, haloalkyl, R b R c amino, R b R c aminoalkyl, R d R e aminoalkanoyl(R b )aminoalkyl, R b R c aminoalkoxy, R b R c aminoalkoxyalkyl, heterocyclo, heterocycloalkyl, heterocyclooxy, heterocyclothio, heteroaryl, heteroarylalkyl, heteroaryloxy, and heteroarylthio, or  
 R 2  and R 3 , together with the carbon to which they are bonded, form a 4- to 8-membered carbocyclic or a 5- or 6-membered heterocyclic ring, wherein each heteroatom in the heterocyclic ring is: 
 independently selected from the group consisting of oxygen, sulfur, and nitrogen,  
 optionally substituted with one or two oxygens when sulfur, and  
 optionally substituted with a substituent selected from the group consisting of C 1 -C 4  hydrocarbyl, C 3 -C 6  cyclohydrocarbyl, C 1 -C 4  hydrocarbylcarbonyl, and C 1 -C 4  hydrocarbylsulfonyl when nitrogen;  
 
   as to R 5  and R 6 : 
 R 5  and R 6  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, acylalkyl, halo, nitro, hydroxyl, cyano, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, R b R c aminoalkyl substituent, thiol, alkylthio, arylthio, cycloalkylthio, cycloalkyloxy, alkoxyalkoxy, heterocyclooxy, and R b R c aminoalkoxy, or  
 R 5  and R 6 , together with the atoms to which they are bonded, form an aliphatic or aromatic carbocyclic or heterocyclic ring having 5- to 7-members;  
   R 20  is selected from the group consisting of —O—R 21 , —NR 13 —O—R 22 , —NR 13 —O—R 14 , and —NR 23 R 24 ;    R 21  is selected from the group consisting of hydrogen, C 1 -C 6 -alkyl, aryl, and aryl-C 1 -C 6 -alkyl;    R 22  is a selectively removable protecting group;    R 13  is selected from the group consisting of hydrogen, C 1 -C 6 -alkyl, and benzyl;    R 14  is selected from the group consisting of hydrogen and C(V)R 15 ;    V is selected from the group consisting of O and S;    R 15  is selected from the group consisting of C 1 -C 6 -alkyl, aryl, C 1 -C 6 -alkoxy, heteroaryl-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, aryloxy, aryl-C 1 -C 6 -alkoxy, aryl-C 1 -C 6 -alkyl, heteroaryl, and amino C 1 -C 6 -alkyl, wherein the amino C 1 -C 6 -alkyl nitrogen is optionally substituted with; 
 up to two substituents independently selected from the group consisting of C 1 -C 6 -alkyl, aryl, aryl-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkoxycarbonyl, and C 1 -C 6 -alkanoyl, or  
 two substituents such that the two substituents, together with the amino nitrogen, form a 5- to 8-membered heterocyclo or heteroaryl ring;  
   as to R 23  and R 24 ; 
 R 23  and R 24  are independently selected from the group consisting of hydrogen, C 1 -C 6 -alkyl, amino C 1 -C 6 -alkyl, hydroxy C 1 -C 6 -alkyl, aryl, and aryl-C 1 -C 6 -alkyl, or  
 R 23  and R 24  together with the nitrogen to which they are bonded, form a 5- to 8-membered ring containing zero or one additional heteroatom selected from the group consisting of oxygen, nitrogen, and sulfur;  
   each R a  is independently selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, R b R c aminoalkanoyl, haloalkanoyl, R b R c aminoalkyl, alkoxyalkyl, haloalkyl, and arylalkoxy;    each R b  and R c  is independently selected from the group consisting of hydrogen, alkanoyl, arylalkyl, aroyl, bisalkoxyalkyl, alkyl, haloalkyl, perfluoroalkoxyalkyl, alkoxyalkyl, cycloalkyl, heterocycloalkyl, heterocycloalkylcarbonyl, aryl, heterocyclo, heteroaryl, cycloalkylalkyl, aryloxyalkyl, heteroaryloxyalkyl, heteroarylalkoxyalkyl, heteroarylthioalkyl, arylsulfonyl, arylalkanoyl, alkylsulfonyl, heteroarylsulfonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, alkyliminocarbonyl, aryliminocarbonyl, heterocycloiminocarbonyl, arylthioalkyl, alkylthioalkyl, arylthioalkenyl, alkylthioalkenyl, heteroarylalkyl, haloalkanoyl, hydroxyalkanoyl, thiolalkanoyl, alkenyl, alkynyl, alkoxycarbonyl, aryloxycarbonyl, aminoalkylcarbonyl, hydroxyalkyl, aminoalkyl, aminoalkylsulfonyl, and aminosulfonyl, wherein any such amino is optionally substituted with: 
 up to two substituents independently selected from the group consisting of alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl, or  
 two substituents such that the two substituents, together with the amino nitrogen, form: 
 a saturated or partially unsaturated heterocyclo group optionally substituted with up to three substituents independently selected from the group consisting of alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl, or  
 a heteroaryl group optionally substituted with up to three independently selected R f  substituents;  
 
   each R d  and R e  is independently selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, alkoxycarbonyl, and arylalkoxycarbonyl; and    each R f  is independently selected from the group consisting of nitro, hydroxy, alkyl, halogen, aryl, alkoxy, cyano, and R d R c amino.    
     
     
         2 . The compound or salt according to  claim 1 , wherein: 
 R 1  is -G-A-R-E-Y;    G is selected from the group consisting of piperidinyl, piperazinyl, and pyrrolidinyl;    A is selected from the group consisting of 
 (1) —O—,  
 (2) —S—,  
 (3) —NR k —,  
 (4) —CO—N(R k )—,  
 (5) —N(R k )—CO—,  
 (6) —CO—O—,  
 (7) —O—CO—,  
 (8) —O—CO—O—,  
 (9) —HC═CH—,  
 (10) —NH—CO—NH—,  
 (11) —C≡C—,  
 (12) —N═N—,  
 (13) —NH—NH—,  
 (14) —CS—N(R k )—,  
 (15) —N(R k )—CS—,  
 (16) —CH 2 —,  
 (17) —O—CH 2 —,  
 (18) —CH 2 —O—,  
 (19) —S—CH 2 —,  
 (20) —CH 2 —S—,  
 (21) —SO—,  
 (22) —SO 2 —, and  
 (23) a bond;  
   R is selected from the group consisting of phenyl, phenylalkyl, phenyloxyalkyl, and phenylthioalkyl, wherein: 
 any phenyl portion of such substituents optionally is substituted with up to two substituents independently selected from the group consisting of halo, alkyl, perfluoroalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, amino, alkoxycarbonylalkyl, alkoxy, C 1 -C 2 -alkylenedioxy, hydroxycarbonylalkyl, hydroxycarbonylalkylamino, nitro, hydroxy, hydroxyalkyl, alkanoylamino, and alkoxycarbonyl;  
   E is selected from the group consisting of: 
 (1) —COR g —,  
 (2) —COR g ,  
 (3) —R g CO—,  
 (4) —CON(R k )—,  
 (5) —(R k )NCO—,  
 (6) —CO—,  
 (7) —SO 2 R g —,  
 (8) —SO 2 R g ,  
 (9) —R g SO 2 —,  
 (10) —SO 2 —,  
 (11) —N(R k )—SO 2 —,  
 (12) —SO 2 —N(R k )—, and  
 (13) a bond;  
   Y is absent or selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, hydroxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkyl, perfluoroalkoxy, perfluoroalkylthio, alkenyl, heterocycloalkyl, alkoxycarbonyl, and aminoalkyl wherein: 
 the aryl, heteroaryl, or heterocycloalkyl is optionally substituted with one or two substituents independently selected from the group consisting of alkanoyl, halo, nitro, arylalkyl, aryl, alkoxy, and amino, wherein: 
 the amino is optionally substituted with one or two substituents independently selected from alkyl and arylalkyl;  
 
   each R g  is independently selected from the group consisting of aryl, heteroaryl, heterocyclo, aroyl, alkanoyl, heteroaroyl, halogen, cyano, aldehydo, hydroxy, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkoxy, aryloxy, heteroaryloxy, alkenyloxy, alkynyloxy, alkoxyaryl, alkoxyheteroaryl, R h R i -amino, alkoxyalkyl, alkylenedioxy, aryloxyalkyl, perfluoroalkyl, trifluoroalkyl, alkylthio, arylthio, alkoxycarbonyl, alkoxycarbonyloxy, aryloxycarbonyl, arylalkoxycarbonyl, arylalkoxycarbonylamino, aryloxycarbonyloxy, carboxy, R h R i -aminocarbonyloxy, R h R i -aminocarbonyl, R h R i -aminoalkanoyl, hydroxyaminocarbonyl, R h R i -aminosulfonyl, R h R i -aminocarbonyl(R h )amino, trifluoromethylsulfonyl(R h )amino, heteroarylsulfonyl(R h )amino, arylsulfonyl(R h )amino, arylsulfonyl(R h )aminocarbonyl, alkylsulfonyl(R h )amino, arylcarbonyl(R h )aminosulfonyl, and alkylsulfonyl(R h )aminocarbonyl;    each R h  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein 
 any such substituent is optionally substituted by up to two independently selected R j  substituents, and  
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted with up to two independently selected R j  substituents;  
   each R i  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein 
 any such substituent is optionally substituted by up to two independently selected R j  substituents, and  
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted with up to two independently selected R j  substituents;  
   each R j  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein: 
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted with up to two substituents independently selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, and alkoxycarbonyl; and  
   each R k  is independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, alkoxycarbonyl, R c R d aminocarbonyl, R c R d aminosulfonyl, R c R d aminoalkanoyl, and R c R d aminoalkysulfonyl.    
     
     
         3 . The compound or salt according to  claim 1 , wherein: 
 R 2  and R 3  are independently selected from the group consisting of hydrogen, hydrocarbyl, hydroxylhydrocarbyl, hydroxyl, amino, dihydrocarbylamino, heterocyclo, heterocyclohydrocarbyl, heterocyclooxy, and heterocyclothio; and    R 5  and R 6  are independently selected from the group consisting of hydrogen, alkyl, hydroxylhydrocarbyl, hydroxyl, and heterocyclooxy.    
     
     
         4 . (canceled).  
     
     
         5 . The compound or salt according to  claim 1 , wherein y is one.  
     
     
         6 . The compound or salt according to  claim 1 , wherein z is one.  
     
     
         7 . The compound or salt according to  claim 1 , wherein the sum of y+z is zero.  
     
     
         8 . The compound or salt according to  claim 1 , wherein R 20  is —NR 13 —O—R 14 .  
     
     
         9 . The compound or salt according to  claim 1 , wherein R 20  is —NR 13 —O—R 22 .  
     
     
         10 . The compound or salt according to  claim 1 , wherein X is —CH 2 —.  
     
     
         11 . The compound or salt according to  claim 1 , wherein X is —NR 9 —.  
     
     
         12 . The compound or salt according to  claim 1 , wherein: 
 R 2  and R 3  are independently selected from the group consisting of hydrogen, C 1 -C 4  hydrocarbyl, hydroxyl, and amino, or    R 2  and R 3 , together with the carbon to which they are bonded, form a 5- or 6-membered heterocyclic ring, wherein each heteroatom in the heterocyclic ring is: 
 independently selected from the group consisting of oxygen, sulfur, and nitrogen,  
 optionally substituted with one or two oxygens when sulfur, and  
 optionally substituted with a substituent selected from the group consisting of C 1 -C 4  hydrocarbyl, C 3 -C 6  cyclohydrocarbyl, C 1 -C 4  hydrocarbylcarbonyl, and C 1 -C 4  hydrocarbylsulfonyl when nitrogen.  
   
     
     
         13 . The compound or salt according to  claim 1 , wherein R 20  is —NHOH.  
     
     
         14 - 17 . (canceled).  
     
     
         18 . A compound or a pharmaceutically acceptable salt thereof, wherein: 
 the compound corresponds in structure to Formula I:                          y and z are each zero or one;    the sum of z+y is one;    the ring structure W is selected from the group consisting of phenyl, pyridinyl, and thienyl;    X is selected from the group consisting of —CH 2 — and —NR 9 —;    R 9  is selected from the group consisting of hydrogen, aryl, alkyl, and arylalkyl;    R 1  is selected from the group consisting of piperidinyl, piperazinyl, and pyrrolidinyl, wherein: 
 the piperidinyl, piperazinyl, and pyrrolidinyl comprise a nitrogen ring atom bonded directly to the depicted SO 2 -group, and  
 the piperidinyl, piperazinyl, and pyrrolidinyl are substituted with a phenyl-containing substituent;  
   R 1  has a length greater than about that of a hexyl group and less than about that of an eicosyl group;    R 1  defines a three-dimensional volume, when rotated about an axis drawn through the SO 2 -bonded 1-position and the 4-position of the piperidinyl or piperazinyl or drawn through the SO 2 -bonded 1-position and the center of 3,4-bond of pyrrolidinyl, 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;    as to R 2  and R 3 : 
 R 2  and R 3  are independently selected from the group consisting of hydrogen, C 1 -C 4  hydrocarbyl, hydroxyl and amino, or  
 R 2  and R 3 , together with the carbon to which they are bonded, form a 5- or 6-membered heterocyclic ring, wherein each heteroatom in the heterocyclic ring is: 
 independently selected from the group consisting of oxygen, sulfur, and nitrogen,  
 optionally substituted with one or two oxygens when sulfur, and  
 optionally substituted with a substituent selected from the group consisting of C 1 -C 4  hydrocarbyl, C 3 -C 6  cyclohydrocarbyl, C 1 -C 4  hydrocarbylcarbonyl, and C 1 -C 4  hydrocarbylsulfonyl when nitrogen; and  
 
   as to R 5  and R 6 : 
 R 5  and R 6  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, acylalkyl, halo, nitro, hydroxyl, cyano, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, R b R c aminoalkyl, thiol, alkylthio, arylthio, cycloalkylthio, cycloalkyloxy, alkoxyalkoxy, heterocyclooxy, and R b R c aminoalkoxy, or  
 R 5  and R 6 , together with the atoms to which they are bonded, form an aliphatic or aromatic carbocyclic or heterocyclic ring having 5- to 7-members.  
   
     
     
         19 . The compound or salt according to  claim 18 , wherein R 1  is selected from the group consisting of piperidinyl, piperazinyl, and pyrrolidinyl, wherein: 
 the piperidinyl, piperazinyl and pyrrolidinyl are substituted with a substituent, R 4 , that has a chain length of up to about 14 carbon atoms.    
     
     
         20 . The compound or salt according to  claim 19 , wherein R 4  is selected from the group consisting of phenyl, phenoxy, phenylthioxy, anilino, phenylazo, phenylureido, benzamido, phenylheterocyclohydrocarbyl, phenylhydrocarbyl, phenylhydrocarbyloxyhydrocarbyl, phenyloxyhydrocarbyl, phenylhydrocarboylhydrocarbyl, phenylcarbonylhydrocarbyl, phenylazophenyl, phenylhydrazinophenyl, hydrocarbylthiophenyl, phenylthiohydrocarbyl, hydrocarbylthiophenylhydrocarbyl, phenylhydrocarbylthiohydrocarbyl, phenylhydrocarbylthiophenyl, and phenylhydrocarbylamino.  
     
     
         21 . The compound or salt according to  claim 19 , wherein R 4  is selected from the group consisting of phenyl, phenoxy, phenthioxy, anilino, phenylazo, phenylureido, benzamido, phenylheterocyclohydrocarbyl, phenylhydrocarbyl, phenylhydrocarbyloxyhydrocarbyl, phenyloxyhydrocarbyl, phenylhydrocarboylhydrocarbyl, phenylcarbonylhydrocarbyl, phenylazophenyl, phenylhydrazinophenyl, hydrocarbylthiophenyl, phenylthiohydrocarbyl, hydrocarbylthiophenylhydrocarbyl, phenylhydrocarbylthiohydrocarbyl, phenylhydrocarbylthiophenyl, and phenylhydrocarbylamino, wherein: 
 each such group is substituted by one or more substituents independently selected from the group consisting of halogen, hydrocarbyl, hydrocarbyloxy, nitro, cyano, perfluorohydrocarbyl, trifluoromethylhydrocarbyl, hydroxy, mercapto, hydroxycarbonyl, aryloxy, arylthio, arylamino, arylhydrocarbyl, aryl, heteroaryloxy, heteroarylthio, heteroarylamino, heteroarhydrocarbyl, hydrocarbyloxycarbonylhydrocarbyl, heterocyclooxy, hydroxycarbonylhydrocarbyl, heterocyclothio, heterocycloamino, cyclohydrocarbyloxy, cyclohydrocarbylthio, cyclohydrocarbylamino, heteroarylhydrocarbyloxy, heteroarylhydrocarbylthio, heteroarylhydrocarbylamino, arylhydrocarbyloxy, arylhydrocarbylthio, arylhydrocarbylamino, heterocyclic, heteroaryl, hydroxycarbonylhydrocarbyloxy, alkoxycarbonylalkoxy, hydrocarbyloyl, arylcarbonyl, arylhydrocarbyloyl, hydrocarboyloxy, arylhydrocarboyloxy, hydroxyhydrocarbyl, hydroxyhydrocarbyloxy, hydrocarbylthio, hydrocarbyloxyhydrocarbylthio, hydrocarbyloxycarbonyl, hydroxycarbonylhydrocarbyloxy, hydrocarbyloxycarbonylhydrocarbyl, hydrocarbylhydroxycarbonyl-hydrocarbylthio, hydrocarbyloxycarbonylhydrocarbyloxy, hydrocarbyloxycarbonylhydrocarbylthio, amino, hydrocarbylcarbonylamino, arylcarbonylamino, cyclohydrocarbylcarbonylamino, heterocyclohydrocarbylcarbonylamino, arylhydrocarbylcarbonylamino, heteroarylcarbonylamino, heteroarylhydrocarbylcarbonylamino, heterocyclohydrocarbyloxy, hydrocarbylsulfonylamino, arylsulfonylamino, arylhydrocarbylsulfonylamino, heteroarylsulfonylamino, heteroarylhydrocarbylsulfonylamino, cyclohydrocarbylsulfonylamino, heterocyclohydrocarbylsulfonylamino, and wherein: 
 the aminohydrocarbyl nitrogen is substituted with up to two substituents independently selected from the group consisting of hydrocarbyl, aryl, arylhydrocarbyl, cyclohydrocarbyl, arylhydrocarbyloxycarbonyl, hydrocarbyloxycarbonyl, and hydrocarboyl, or  
 the aminohydrocarbyl nitrogen is substituted with two substituents such that the two substituents, together with the aminohydrocarbyl nitrogen, form a 5- to 8-membered heterocyclic or heteroaryl ring.  
   
     
     
         22 . The compound or salt according to  claim 18 , wherein R 1  is selected from the group consisting of piperidinyl, piperazinyl, and pyrrolidinyl, wherein: 
 the piperidinyl, piperazinyl, and pyrrolidinyl are substituted with a substituent selected from the group consisting of phenyl, phenoxy, phenylthioxy, phenylazo, phenylureido, anilino, and benzamido.    
     
     
         23 . (canceled).  
     
     
         24 . (currently amended) The compound or salt according to  claim 18 , wherein z is one and y is zero.  
     
     
         25 . The compound or salt according to  claim 18 , wherein y is one and z is zero.  
     
     
         26 . The compound or salt according to  claim 18 , wherein R 1  has a length greater than that of an octyl group and less than that of a stearyl group.  
     
     
         27 . A compound or a pharmaceutically acceptable salt thereof, wherein: 
 the compound corresponds to Formula II-1 or III-1,                          the ring structure W is selected from the group consisting of phenyl, pyridinyl, and thienyl;    R 1  is selected from the group consisting of piperidinyl, piperazinyl, and pyrrolidinyl, 
 the piperidinyl, piperazinyl, and pyrrolidinyl comprises a nitrogen ring atom bonded directly to the depicted SO 2 -group, and  
 the piperidinyl, piperazinyl, and pyrrolidinyl are substituted with a phenyl-containing substituent;  
   R 1  has a length greater than about that of a hexyl group and less than about that of an eicosyl group;    R 1  defines a three-dimensional volume, when rotated about an axis drawn through the SO 2 -bonded 1-position and the 4-position of the piperidinyl or piperazinyl or drawn through the SO 2 -bonded 1-position and the center of 3,4-bond of the pyrrolidinyl, 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,    as to R 2  and R 3 : 
 R 2  and R 3  are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, R a oxyalkyl, hydroxyl, thiol, R a thioalkyl, haloalkyl, R b R c amino, R b R c aminoalkyl, R d R e aminoalkanoyl(R b )aminoalkyl, R b R c aminoalkoxyalkyl, heterocyclo, heterocycloalkyl, heterocyclooxy, heterocyclothio, heteroaryl, heteroarylalkyl, heteroaryloxy, and heteroarylthio, or  
 R 2  and R 3 , together with the carbon to which they are bonded, form a 4- to 8-membered carbocyclic or 5- or 6-membered heterocyclic ring, wherein each heteroatom is: 
 independently selected from the group consisting of oxygen, sulfur, and nitrogen,  
 optionally substituted with one or two oxygens when sulfur, and  
 optionally substituted with a substituent selected from the group consisting of C 1 -C 4  hydrocarbyl, C 3 -C 6  cyclohydrocarbyl, C 1 -C 4  hydrocarbylcarbonyl, and C 1 -C 4  hydrocarbylsulfonyl when nitrogen;  
 
   as to R 5  and R 6 : 
 R 5  and R 6  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, acylalkyl, halo, nitro, hydroxyl, cyano, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, R b R c aminoalkyl, thiol, alkylthio, arylthio, cycloalkylthio, cycloalkyloxy, alkoxyalkoxy, heterocyclooxy, and R b R c aminoalkoxy, or  
 R 5  and R 6  together with the atoms to which they are bonded form an aliphatic or aromatic carbocyclic or heterocyclic ring having 5- to 7-members;  
   each R a  is independently selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, R b R c aminoalkanoyl, haloalkanoyl, R b R c aminoalkyl, alkoxyalkyl, haloalkyl, and arylalkoxy;    each R b  and R c  is independently selected from the group consisting of hydrogen, alkanoyl, arylalkyl, aroyl, bisalkoxyalkyl, alkyl, haloalkyl, perfluoroalkoxyalkyl, alkoxyalkyl, cycloalkyl, heterocycloalkyl, heterocycloalkylcarbonyl, aryl, heterocyclo, heteroaryl, cycloalkylalkyl, aryloxyalkyl, heteroaryloxyalkyl, heteroarylalkoxyalkyl, heteroarylthioalkyl, arylsulfonyl, arylalkanoyl, alkylsulfonyl, heteroarylsulfonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, alkyliminocarbonyl, aryliminocarbonyl, heterocycloiminocarbonyl, arylthioalkyl, alkylthioalkyl, arylthioalkenyl, alkylthioalkenyl, heteroarylalkyl, haloalkanoyl, hydroxyalkanoyl, thiolalkanoyl, alkenyl, alkynyl, alkoxycarbonyl, aryloxycarbonyl, aminoalkylcarbonyl, hydroxyalkyl, aminoalkyl, aminoalkylsulfonyl, and aminosulfonyl, wherein any amino of R b  and R c  is optionally substituted with: 
 up to two substituents independently selected from the group consisting of alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl, or  
 two substituents such that the two substituents, together with the amino nitrogen, form: 
 a saturated or partially unsaturated heterocyclo group optionally substituted with up to three substituents independently selected from the group consisting of alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl or  
 a heteroaryl group optionally substituted with up to three independently selected R f  substituents;  
 
   each R d  and R e  is independently selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl;    each R f  is independently selected from the group consisting of nitro, hydroxy, alkyl, halogen, aryl, alkoxy, cyano, and R d R e amino.    
     
     
         28 . The compound or salt according to  claim 27 , wherein: 
 R 1  is -G-A-R-E-Y;    G is selected from the group consisting of piperidinyl, piperazinyl, and pyrrolidinyl;    A is selected from the group consisting of: 
 (1) —O—,  
 (2) —S—,  
 (3) —NR k —,  
 (4) —CO—N(R k )—,  
 (5) —N(R k )—CO—,  
 (6) —CO—O—,  
 (7) —O—CO—,  
 (8) —O—CO—O—,  
 (9) —HC═CH—,  
 (10) —NH—CO—NH—,  
 (11) —C≡C—,  
 (12) —N═N—,  
 (13) —NH—NH—,  
 (14) —CS—N(R k )—,  
 (15) —N(R k )—CS—,  
 (16) —CH 2 —,  
 (17) —O—CH 2 —,  
 (18) —CH 2 —O—,  
 (19) —S—CH 2 —,  
 (20) —CH 2 —S—,  
 (21) —SO—,  
 (22) —SO 2 —, and  
 (23) a bond;  
   R is selected from the group consisting of phenyl, phenylalkyl, phenyloxyalkyl, and phenylthioalkyl, wherein: 
 any phenyl portion of such substituents is optionally substituted with up to two substituents independently selected from the group consisting of halo, alkyl, perfluoroalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, amino, alkoxycarbonylalkyl, alkoxy, C 1 -C 2 -alkylenedioxy, hydroxycarbonylalkyl, hydroxycarbonylalkylamino, nitro, hydroxy, hydroxyalkyl, alkanoylamino, and alkoxycarbonyl;  
   E is selected from the group consisting of: 
 (1) —COR g —,  
 (2) —COR g ,  
 (3) —R g CO—,  
 (4) —CON(R k )—,  
 (5) —(R k )NCO—,  
 (6) —CO—,  
 (7) —SO 2 R g —,  
 (8) —SO 2 R g ,  
 (9) —R g SO 2 —,  
 (10) —SO 2 —,  
 (11) —N(R k )—SO 2 —,  
 (12) —SO 2 —N(R k )—, and  
 (13) a bond;  
   Y is absent or selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, hydroxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, alkenyl, heterocycloalkyl, alkoxycarbonyl, and aminoalkyl, wherein: 
 the aryl, heteroaryl, or heterocycloalkyl group is optionally substituted with up to two substituents independently selected from the group consisting of alkanoyl, halo, nitro, arylalkyl, aryl, alkoxy, and amino, wherein: 
 the amino is optionally substituted with up to two substituents independently selected from alkyl and arylalkyl;  
 
   each R g  is independently selected from the group consisting of aryl, heteroaryl, heterocyclo, aroyl, alkanoyl, heteroaroyl, halogen, cyano, aldehydo, hydroxy, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkoxy, aryloxy, heteroaryloxy, alkenyloxy, alkynyloxy, alkoxyaryl, alkoxyheteroaryl, R h R i -amino, alkoxyalkyl, alkylenedioxy, aryloxyalkyl, perfluoroalkyl, trifluoroalkyl, alkylthio, arylthio, alkoxycarbonyl, alkoxycarbonyloxy, aryloxycarbonyl, arylalkoxycarbonyl, arylalkoxycarbonylamino, aryloxycarbonyloxy, carboxy, R h R i -aminocarbonyloxy, R h R i -aminocarbonyl, R h R i -aminoalkanoyl, hydroxyaminocarbonyl, R h R i -aminosulfonyl, R h R i -aminocarbonyl(R h )amino, trifluoromethylsulfonyl(R h )amino, heteroarylsulfonyl(R h )amino, arylsulfonyl(R h )amino, arylsulfonyl(R h )aminocarbonyl, alkylsulfonyl(R h )amino, arylcarbonyl(R h )aminosulfonyl, and alkylsulfonyl(R h )aminocarbonyl;    each R h  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein: 
 each such substituent is optionally substituted by up to two independently selected R j  substituents,  
 the amino of the aminoalkyl or and aminoalkanoyl is optionally substituted with up to two independently selected R j  substituents;  
   each R i  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein: 
 each such substituent is optionally substituted by up to two independently selected R j  substituents, and  
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted with up to two independently selected R j  substituents;  
   each R j  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein: 
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted with up to 2 substituents independently selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, and alkoxycarbonyl; and  
   each R k  is independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, alkoxycarbonyl, R c R d aminocarbonyl, R c R d aminosulfonyl, R c R d aminoalkanoyl, and R c R d aminoalkysulfonyl.    
     
     
         29 . The compound or salt according to  claim 27 , wherein: 
 R 2  and R 3  are independently selected from the group consisting of hydrogen, C 1 -C 4  hydrocarbyl, hydroxyl, and amino, or    R 2  and R 3 , together with the carbon to which they are bonded, form a 5- or 6-membered heterocyclic ring, wherein each heteroatom of the heterocyclic ring is: 
 independently selected from the group consisting of oxygen, sulfur, and nitrogen,  
 optionally substituted with one or two oxygens when sulfur, and  
 optionally substituted with a substituent selected from the group consisting of C 1 -C 4  hydrocarbyl, C 3 -C 6  cyclohydrocarbyl, C 1 -C 4  hydrocarbylcarbonyl, and C 1 -C 4  hydrocarbylsulfonyl when nitrogen.  
   
     
     
         30 . The compound or salt according to  claim 27 , wherein the compound corresponds in structure to Formula II or Formula III:  
       
         
           
           
               
               
           
         
       
     
     
         31 . The compound or salt according to  claim 30 , wherein: 
 R 1  is selected from the group consisting of piperidinyl, piperazinyl, and pyrrolidinyl, wherein: 
 the piperidinyl, piperazinyl, or pyrrolidinyl is substituted at its own 4-position when piperidinyl or piperazinyl and at its own 3- or 4-position when pyrrolidinyl with a substituent, R 4 , selected from the group consisting of phenyl, phenoxy, phenylthioxy, phenylazo, phenylureido, anilino, and benzamido; and  
   as to R 2  and R 3 : 
 R 2  and R 3  are independently selected from the group consisting of hydrogen, C 1 -C 4  hydrocarbyl, hydroxyl, and amino, or  
 R 2  and R 3 , together with the carbon to which they are bonded, form a 5- or 6-membered heterocyclic ring, wherein each heteroatom of the heterocyclic ring is: 
 independently selected from the group consisting of oxygen, sulfur, and nitrogen,  
 optionally substituted with one or two oxygens when sulfur, and  
 optionally substituted with a substituent selected from the group consisting of C 1 -C 4  hydrocarbyl, C 3 -C 6  cyclohydrocarbyl, C 1 -C 4  hydrocarbylcarbonyl, and C 1 -C 4  hydrocarbylsulfonyl when nitrogen.  
 
   
     
     
         32 . The compound or salt according to  claim 30 , wherein: 
 R 1  is selected from the group consisting of piperidinyl, piperazinyl, and pyrrolidinyl, wherein: 
 the piperidinyl, piperazinyl, or pyrrolidinyl is substituted at its own 4-position when piperidinyl or piperazinyl and at its own 3- or 4-position when pyrrolidinyl with a substituent, R 4 , selected from the group consisting of phenyl, phenoxy, anilino, phenylthioxy, benzamido, and phenylureido, wherein the phenyl of any such substituent is optionally substituted:  
 at the meta or para position or both with a substituent that is selected from the group consisting of halogen, C 1 -C 9  hydrocarbyloxy, C 1 -C 10  hydrocarbyl, di-C 1 -C 9  hydrocarbylamino, carboxyl C 1 -C 8  hydrocarbyl, C 1 -C 4  hydrocarbyloxy carbonyl C 1 -C 4  hydrocarbyl, a C 1 -C 4  hydrocarbyloxycarbonyl C 1 -C 4  hydrocarbyl, and carboxamido C 1 -C 8  hydrocarbyl, or  
 at the meta- and para-positions by two methyl groups or C 1 -C 2  alkylenedioxy.  
   
     
     
         33 . The compound or salt according to  claim 32 , wherein R 4  is unsubstituted phenoxy or unsubstituted phenylthioxy.  
     
     
         34 . The compound or salt according to  claim 30 , wherein the compound corresponds in structure to Formula II.  
     
     
         35 . The compound or salt according to  claim 30 , wherein the compound corresponds in structure to Formula III.  
     
     
         36 . The compound or salt according to  claim 30 , wherein R 2  and R 3 , together with the carbon to which they are bonded, form a 4-tetrahydropyranyl or 4-piperidinyl, wherein: 
 the 4-piperidinyl is optionally substituted with a substituent, R 10 , selected from the group consisting of C 1 -C 4  hydrocarbyl, C 3 -C 6  cyclohydrocarbyl, C 1 -C 4  hydrocarbylcarbonyl, and C 1 -C 4  hydrocarbylsulfonyl.    
     
     
         37 . The compound or salt according to  claim 36 , wherein the compound corresponds in structure to Formula IV:  
       
         
           
           
               
               
           
         
       
     
     
         38 . A compound or a pharmaceutically acceptable salt thereof, wherein: 
 the compound corresponds in structure to Formula V:                          the ring structure W is selected from the group consisting of phenyl, pyridinyl, and thienyl;    R 1  is selected from the group consisting of piperidinyl, piperazinyl, and pyrrolidinyl, wherein: 
 the piperidinyl, piperazinyl, and pyrrolidinyl comprise a nitrogen ring atom bonded directly to the depicted SO 2 -group, and  
 the piperidinyl, piperazinyl, and pyrrolidinyl are substituted with a phenyl-containing substituent;  
   R 1  has a length greater than about that of a hexyl group and less than about that of an eicosyl group;    R 1  defines a three-dimensional volume, when rotated about an axis drawn through the SO 2 -bonded 1-position and the 4-position of the piperidinyl or piperazinyl or drawn through the SO 2 -bonded 1-position and the center of 3,4-bond of the pyrrolidinyl, 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;    each R g  is independently selected from the group consisting of aryl, heteroaryl, heterocyclo, aroyl, alkanoyl, heteroaroyl, halogen, cyano, aldehydo, hydroxy, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkoxy, aryloxy, heteroaryloxy, alkenyloxy, alkynyloxy, alkoxyaryl, alkoxyheteroaryl, R h R i -amino, alkoxyalkyl, alkylenedioxy, aryloxyalkyl, perfluoroalkyl, trifluoroalkyl, alkylthio, arylthio, alkoxycarbonyl, alkoxycarbonyloxy, aryloxycarbonyl, arylalkoxycarbonyl, arylalkoxycarbonylamino, aryloxycarbonyloxy, carboxy, R h R i -aminocarbonyloxy, R h R i -aminocarbonyl, R h R i -aminoalkanoyl, hydroxyaminocarbonyl, R h R i -aminosulfonyl, R h R i -aminocarbonyl(R h )amino, trifluoromethylsulfonyl(R h )amino, heteroarylsulfonyl(R h )amino, arylsulfonyl(R h )amino, arylsulfonyl(R h )aminocarbonyl, alkylsulfonyl(R h )amino, arylcarbonyl(R h )aminosulfonyl, and alkylsulfonyl(R h )aminocarbonyl;    each R h  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein: 
 any such substituent is optionally substituted with up to two substituents independently selected from R j  substituents, and  
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted by up to two independently selected R j  substituents;  
   each R i  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein: 
 any such substituent is optionally substituted by up to two independently selected R j  substituents, and  
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted with up to two independently selected R j  substituents; and  
   each R j  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein: 
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted with up to two substituents independently selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, and alkoxycarbonyl.  
   
     
     
         39 . The compound or salt according to  claim 36 , wherein: 
 the compound corresponds in structure to Formula VA:                              and    R 10  is selected from the group consisting of C 1 -C 4  hydrocarbyl, C 3 -C 6  cyclohydrocarbyl, C 1 -C 4  hydrocarbylcarbonyl, and C 1 -C 4  hydrocarbylsulfonyl.    
     
     
         40 . The compound or salt according to  claim 36 , wherein W is selected from the group consisting of phenyl and pyridinyl.  
     
     
         41 - 42 . (canceled).  
     
     
         43 . A compound or a pharmaceutically acceptable salt thereof, wherein: 
 the compound corresponds in structure to Formula VIA:                          ring structure W 2 , including the depicted nitrogen, is selected from the group consisting of piperidinyl, piperazinyl, and pyrrolidinyl;    R 4  is a phenyl-containing substituent bonded at the 4-position (relative to the depicted nitrogen) when W 2  is piperidinyl or piperazinyl and at the 3- or 4-position (relative to the depicted nitrogen) when W 2  is pyrrolidinyl;    R 4  has a chain length of up to about 14 carbon atoms;    as to R 5  and R 6 : 
 R 5  and R 6  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, acylalkyl, halo, nitro, hydroxyl, cyano, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, R b R c aminoalkyl, thiol, alkylthio, arylthio, cycloalkylthio, cycloalkyloxy, alkoxyalkoxy, heterocyclooxy, and R b R c aminoalkoxy, or  
 R 5  and R 6 , together with the atoms to which they are bonded, form an aliphatic or aromatic carbocyclic or heterocyclic ring having 5 to 7-members;  
   R 20  is selected from the group consisting of —O—R 21 , —NR 13 —O—R 22 , —NR 13 —OR 14 , and —NR 23 R 24 ;    R 21  is selected from the group consisting of hydrogen, C 1 -C 6 -alkyl, aryl, and aryl-C 1 -C 6 -alkyl;    R 22  is a selectively removable protecting group;    R 13  is selected from the group consisting of hydrogen, C 1 -C 6 -alkyl, and benzyl;    R 14  is selected from the group consisting of hydrogen and C(V)R 15 ;    V is selected from the group consisting of O and S;    R 15  is selected from the group consisting of C 1 -C 6 -alkyl, aryl, C 1 -C 6 -alkoxy, heteroaryl-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, aryloxy, aryl-C 1 -C 6 -alkoxy, aryl-C 1 -C 6 -alkyl, heteroaryl, and amino C 1 -C 6 -alkyl, wherein the amino C 1 -C 6 -alkyl nitrogen is optionally substituted with: 
 up to two substituents independently selected from the group consisting of C 1 -C 6 -alkyl, aryl, aryl-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkoxycarbonyl, and C 1 -C 6 -alkanoyl, or  
 two substituents such that the two substituents, together with the amino, form a 5- to 8-membered heterocyclo or heteroaryl ring;  
   as to R 23  and R 24 : 
 R 23  and R 24  are independently selected from the group consisting of hydrogen, C 1 -C 6 -alkyl, amino C 1 -C 6 -alkyl, hydroxy C 1 -C 6 -alkyl, aryl, and aryl-C 1 -C 6 -alkyl, or  
 R 23  and R 24  together with the depicted nitrogen, form a 5- to 8-membered ring containing zero or one additional heteroatom that is selected from the group consisting of oxygen, nitrogen, and sulfur;  
   each R b  and R c  is independently selected from the group consisting of hydrogen, alkanoyl, arylalkyl, aroyl, bisalkoxyalkyl, alkyl, haloalkyl, perfluoroalkoxyalkyl, alkoxyalkyl, cycloalkyl, heterocycloalkyl, heterocycloalkylcarbonyl, aryl, heterocyclo, heteroaryl, cycloalkylalkyl, aryloxyalkyl, heteroaryloxyalkyl, heteroarylalkoxyalkyl, heteroarylthioalkyl, arylsulfonyl, arylalkanoyl, alkylsulfonyl, heteroarylsulfonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, alkyliminocarbonyl, aryliminocarbonyl, heterocycloiminocarbonyl, arylthioalkyl, alkylthioalkyl, arylthioalkenyl, alkylthioalkenyl, heteroarylalkyl, haloalkanoyl, hydroxyalkanoyl, thiolalkanoyl, alkenyl, alkynyl, alkoxycarbonyl, aryloxycarbonyl, aminoalkylcarbonyl, hydroxyalkyl, aminoalkyl, aminoalkylsulfonyl, and aminosulfonyl, wherein any amino of R b  or R c  is optionally substituted with: 
 up to two substituents independently selected from the group consisting of alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl, or  
 two substituents such that the substituents, together with the amino nitrogen, form: 
 a saturated or partially unsaturated heterocyclo group optionally substituted with up to three substituents independently selected from the group consisting of alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl, or  
 a heteroaryl group optionally substituted with up to three independently selected R f  substituents;  
 
   each R d  and R e  is independently selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl; and    each R f  is independently selected from the group consisting of nitro, hydroxy, alkyl, halogen, aryl, alkoxy, cyano, and R d R c amino.    
     
     
         44 . The compound or salt according to  claim 43 , wherein R 4  is selected from the group consisting of phenyl, phenoxy, phenylthioxy, anilino, phenylazo, phenylureido, benzamido, phenylheterocyclohydrocarbyl, phenylhydrocarbyl, phenylhydrocarbyloxyhydrocarbyl, phenyloxyhydrocarbyl, phenylhydrocarboylhydrocarbyl, phenylcarbonylhydrocarbyl, phenylhydrazinophenyl, hydrocarbylthiophenyl, hydrocarbylthiophenyl, hydrocarbylthiophenylhydrocarbyl, phenylhydrocarbylthiohydrocarbyl, phenylhydrocarbylthiophenyl, and phenylhydrocarbylamino.  
     
     
         45 . The compound or salt according to  claim 43 , wherein R 4  is selected from the group consisting of phenyl, phenoxy, phenylthioxy, anilino, phenylazo, phenylureido, benzamido, phenylheterocyclohydrocarbyl, phenylhydrocarbyl, phenylhydrocarbyloxyhydrocarbyl, phenyloxyhydrocarbyl, phenylhydrocarboylhydrocarbyl, phenylcarbonylhydrocarbyl, phenylazophenyl, phenylhydrazinophenyl, hydrocarbylthiophenyl, phenylthiohydrocarbyl, hydrocarbylthiophenylhydrocarbyl, phenylhydrocarbylthiohydrocarbyl, phenylhydrocarbylthiophenyl, and phenylhydrocarbylamino, wherein: 
 any such substituent is substituted by one or more substituents independently selected from the group consisting of halogen, hydrocarbyl, hydrocarbyloxy, nitro, cyano, perfluorohydrocarbyl, trifluoromethylhydrocarbyl, hydroxy, mercapto, hydroxycarbonyl, aryloxy, arylthio, arylamino, arylhydrocarbyl, aryl, heteroaryloxy, heteroarylthio, heteroarylamino, heteroarhydrocarbyl, hydrocarbyloxycarbonylhydrocarbyl, heterocyclooxy, hydroxycarbonylhydrocarbyl, heterocyclothio, heterocycloamino, cyclohydrocarbyloxy, cyclohydrocarbylthio, cyclohydrocarbylamino, heteroarylhydrocarbyloxy, heteroarylhydrocarbylthio, heteroarylhydrocarbylamino, arylhydrocarbyloxy, arylhydrocarbylthio, arylhydrocarbylamino, heterocyclic, heteroaryl, hydroxycarbonylhydrocarbyloxy, alkoxycarbonylalkoxy, hydrocarbyloyl, arylcarbonyl, arylhydrocarbyloyl, hydrocarboyloxy, arylhydrocarboyloxy, hydroxyhydrocarbyl, hydroxyhydrocarbyloxy, hydrocarbylthio, hydrocarbyloxyhydrocarbylthio, hydrocarbyloxycarbonyl, hydroxycarbonylhydrocarbyloxy, hydrocarbyloxycarbonylhydrocarbyl, hydrocarbylhydroxycarbonyl-hydrocarbylthio, hydrocarbyloxycarbonylhydrocarbyloxy, hydrocarbyloxycarbonylhydrocarbylthio, amino, hydrocarbylcarbonylamino, arylcarbonylamino, cyclohydrocarbylcarbonylamino, heterocyclohydrocarbylcarbonylamino, arylhydrocarbylcarbonylamino, heteroarylcarbonylamino, heteroarylhydrocarbylcarbonylamino, heterocyclohydrocarbyloxy, hydrocarbylsulfonylamino, arylsulfonylamino, arylhydrocarbylsulfonylamino, heteroarylsulfonylamino, heteroarylhydrocarbylsulfonylamino, cyclohydrocarbylsulfonylamino, heterocyclohydrocarbylsulfonylamino, and aminohydrocarbyl, wherein: 
 the aminohydrocarbyl nitrogen is substituted with up to two substituents independently selected from the group consisting of hydrocarbyl, aryl, arylhydrocarbyl, cyclohydrocarbyl, arylhydrocarbyloxycarbonyl, hydrocarbyloxycarbonyl, and hydrocarboyl, or  
 the aminohydrocarbyl nitrogen is substituted with two substituents such that the two substituents, together with the aminohydrocarbyl nitrogen, form a 5- to 8-membered heterocyclic or heteroaryl ring.  
   
     
     
         46 . The compound or salt according to  claim 43 , wherein R 20  is —NR 13 —O—R 14 .  
     
     
         47 . The compound or salt according to  claim 46 , wherein R 13  is hydrogen.  
     
     
         48 . The compound or salt according to  claim 43 , wherein R 20  is —NR 13 —O—R 22 .  
     
     
         49 . The compound or salt according to  claim 48 , wherein: 
 R 13  is hydrogen, and    R 22  is selected from the group consisting of 2-tetrahydropyranyl, benzyl, p-methoxybenzyl, C 1 -C 6 -alkoxycarbonyl, trisubstituted silyl, o-nitrophenyl, and peptide synthesis resin, wherein: 
 the trisubstituted silyl is substituted with C 1 -C 6 -alkyl; aryl; aryl-C 1 -C 6 -alkyl; or a mixture of C 1 -C 6 -alkyl, aryl, and/or aryl-C 1 -C 6 -alkyl.  
   
     
     
         50 . The compound or salt according to  claim 43 , wherein the compound corresponds in structure to Formula VIA-1,  
       
         
           
           
               
               
           
         
       
     
     
         51 . A compound or a pharmaceutically acceptable salt thereof, wherein: 
 the compound corresponds in structure to Formula VIIC,                          ring structure W 2 , including the depicted nitrogen, is selected from the group consisting of piperidinyl, piperazinyl, and pyrrolidinyl;    -A-R-E-Y is a substituent bonded at the 4-position (relative to the depicted nitrogen of W 2 ) when W 2  is piperadinyl or piperazinyl and at the 3- or 4-position (relative to the depicted nitrogen of W 2 ) when W 2  is pyrrolidinyl;    A is selected from the group consisting of: 
 (1) —O—,  
 (2) —S—,  
 (3) —NR k —,  
 (4) —CO—N(R k )—,  
 (5) —N(R k )—CO—,  
 (6) —CO—O—,  
 (7) —O—CO—,  
 (8) —O—CO—O—,  
 (9) —HC═CH—,  
 (10) —NH—CO—NH—,  
 (11) —C≡C—,  
 (12) —N═N—,  
 (13) —NH—NH—,  
 (14) —CS—N(R k )—,  
 (15) —N(R k )—CS—,  
 (16) —CH 2 —,  
 (17) —O—CH 2 —,  
 (18) —CH 2 —O—,  
 (19) —S—CH 2 —,  
 (20) —CH 2 —S—,  
 (21) —SO—,  
 (22) —SO 2 —, and  
 (23) a bond;  
   R is selected from the group consisting of phenyl, phenylalkyl, phenyloxyalkyl, and phenylthioalkyl, wherein: 
 any phenyl portion of such substituents is optionally substituted with up to two substituents independently selected from the group consisting of halo, alkyl, perfluoroalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, amino, alkoxycarbonylalkyl, alkoxy, C 1 -C 2 -alkylenedioxy, hydroxycarbonylalkyl, hydroxycarbonylalkylamino, nitro, hydroxy, hydroxyalkyl, alkanoylamino, and alkoxycarbonyl;  
   E is selected from the group consisting of: 
 (1) —COR g —,  
 (2) —COR g ,  
 (3) —R g CO—,  
 (4) —CON(R k )—,  
 (5) —(R k )NCO—,  
 (6) —CO—,  
 (7) —SO 2 R g —,  
 (8) —SO 2 R g ,  
 (9) —R g SO 2 —,  
 (10) —SO 2 —,  
 (11) —N(R k )—SO 2 —,  
 (12) —SO 2 —N(R k )—, and  
 (13) a bond;  
   Y is absent or selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, hydroxy, nitrile, nitro, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkyl, R a oxyalkyl, perfluoroalkoxy, perfluoroalkylthio, alkenyl, heterocycloalkyl, alkoxycarbonyl, and aminoalkyl, wherein: 
 the aryl, heteroaryl, or heterocycloalkyl is optionally substituted with up to two substituents independently selected from the group consisting of alkanoyl, halo, nitro, nitrile, haloalkyl, alkyl, arylalkyl, aryl, alkoxy, and amino, wherein: 
 the amino is optionally substituted with up to two substituents independently selected from the group consisting of alkyl and arylalkyl;  
 
   each R a  is independently selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, R b R c aminoalkanoyl, haloalkanoyl, R b R c aminoalkyl, alkoxyalkyl, haloalkyl, and arylalkoxy;    each R b  and R c  is independently selected from the group consisting of hydrogen, alkanoyl, arylalkyl, aroyl, bisalkoxyalkyl, alkyl, haloalkyl, perfluoroalkoxyalkyl, alkoxyalkyl, cycloalkyl, heterocycloalkyl, heterocycloalkylcarbonyl, aryl, heterocyclo, heteroaryl, cycloalkylalkyl, aryloxyalkyl, heteroaryloxyalkyl, heteroarylalkoxyalkyl, heteroarylthioalkyl, arylsulfonyl, arylalkanoyl, alkylsulfonyl, heteroarylsulfonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, alkyliminocarbonyl, aryliminocarbonyl, heterocycloiminocarbonyl, arylthioalkyl, alkylthioalkyl, arylthioalkenyl, alkylthioalkenyl, heteroarylalkyl, haloalkanoyl, hydroxyalkanoyl, thiolalkanoyl, alkenyl, alkynyl, alkoxycarbonyl, aryloxycarbonyl, aminoalkylcarbonyl, hydroxyalkyl, aminoalkyl, aminoalkylsulfonyl, and aminosulfonyl, wherein any amino of R b  and R c  is optionally substituted with: 
 up to two substituents independently selected from the group consisting of alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl, or  
 two substituents such that the two substituents, taken together with the amino nitrogen, form: 
 a saturated or partially unsaturated heterocyclo group optionally substituted with up to three substituents independently selected from the group consisting of alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl, or  
 a heteroaryl group optionally substituted with up to three independently selected R f  substituents;  
 
   each R d  and R e  is independently selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl;    each R f  is independently selected from the group consisting of nitro, hydroxy, alkyl, halogen, aryl, alkoxy, cyano, and R d R e amino;    each R g  is independently selected from the group consisting of aryl, heteroaryl, heterocyclo, aroyl, alkanoyl, heteroaroyl, halogen, cyano, aldehydo, hydroxy, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkoxy, aryloxy, heteroaryloxy, alkenyloxy, alkynyloxy, alkoxyaryl, alkoxyheteroaryl, R h R i -amino, alkoxyalkyl, alkylenedioxy, aryloxyalkyl, perfluoroalkyl, trifluoroalkyl, alkylthio, arylthio, alkoxycarbonyl, alkoxycarbonyloxy, aryloxycarbonyl, arylalkoxycarbonyl, arylalkoxycarbonylamino, aryloxycarbonyloxy, carboxy, R h R i -aminocarbonyloxy, R h R i -aminocarbonyl, R h R i -aminoalkanoyl, hydroxyaminocarbonyl, R h R i -aminosulfonyl, R h R i -aminocarbonyl(R h )amino, trifluoromethylsulfonyl(R h )amino, heteroarylsulfonyl(R h )amino, arylsulfonyl(R h )amino, arylsulfonyl(R h )aminocarbonyl, alkylsulfonyl(R h )amino, arylcarbonyl(R h )aminosulfonyl, and alkylsulfonyl(R h )aminocarbonyl;    each R h  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein: 
 any such substituent is optionally substituted by up to two substituents independently selected from R j  substituents, and  
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted with up to two independently selected R j  substituents;  
   each R i  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein: 
 any such substituent is optionally substituted by up to two independently selected R j  substituents, and  
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted with up to two independently selected R j  substituents;  
   each R j  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein: 
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted with up to two substituents independently selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, and alkoxycarbonyl; and  
   each R k  is independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, alkoxycarbonyl, R c R d aminocarbonyl, R c R d aminosulfonyl, R c R d aminoalkanoyl, and R c R d aminoalkysulfonyl.    
     
     
         52 . A compound or a pharmaceutically acceptable salt thereof, wherein: 
 the compound corresponds to Formula VIIB:                          G is selected from the group consisting of piperidinyl, piperazinyl, and pyrrolidinyl, wherein: 
 the piperidinyl, piperazinyl, and pyrrolidinyl comprises a nitrogen ring atom bonded to the depicted sulfonyl group;  
   A is selected from the group consisting of: 
 (1) —O—,  
 (2) —S—,  
 (3) —NR k —,  
 (4) —CO—N(R k )—,  
 (5) —N(R k )—CO—,  
 (6) —CO—O—,  
 (7) —O—CO—,  
 (8) —O—CO—O—,  
 (9) —HC═CH—,  
 (10) —NH—CO—NH—,  
 (11) —C≡C—,  
 (12) —N═N—,  
 (13) —NH—NH—,  
 (14) —CS—N(R k )—,  
 (15) —N(R k )—CS—,  
 (16) —CH 2 —,  
 (17) —O—CH 2 —,  
 (18) —CH 2 —O—,  
 (19) —S—CH 2 —,  
 (20) —CH 2 —S—,  
 (21) —SO—,  
 (22) —SO 2 —, and  
 (23) a bond;  
   R is selected from the group consisting of phenyl, phenylalkyl, phenyloxyalkyl, and phenylthioalkyl, wherein: 
 any phenyl portion of such substituents is optionally substituted with up to two substituents independently selected from the group consisting of halo, alkyl, perfluoroalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, amino, alkoxycarbonylalkyl, alkoxy, C 1 -C 2 -alkylenedioxy, hydroxycarbonylalkyl, hydroxycarbonylalkylamino, nitro, hydroxy, hydroxyalkyl, alkanoylamino, and alkoxycarbonyl;  
   E is selected from the group consisting of: 
 (1) —COR g —,  
 (2) —COR g ,  
 (3) —R g CO—,  
 (4) —CON(R k )—,  
 (5) —(R k )NCO—,  
 (6) —CO—,  
 (7) —SO 2 R g —,  
 (8) —SO 2 R g ,  
 (9) —R g SO 2 —,  
 (10) —SO 2 —,  
 (11) —N(R k )—SO 2 —,  
 (12) —SO 2 —N(R k )—, and  
 (13) a bond;  
   Y is absent or selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, hydroxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkyl, perfluoroalkoxy, perfluoroalkylthio, alkenyl, heterocycloalkyl, alkoxycarbonyl, and aminoalkyl, wherein: 
 the aryl, heteroaryl, or heterocycloalkyl is optionally substituted with up to two substituents independently selected from the group consisting of alkanoyl, halo, nitro, arylalkyl, aryl, alkoxy, and amino, wherein: 
 the amino is substituted with up to two substituents independently selected from alkyl and arylalkyl;  
 
   each R b  and R c  is independently selected from the group consisting of hydrogen, alkanoyl, arylalkyl, aroyl, bisalkoxyalkyl, alkyl, haloalkyl, perfluoroalkoxyalkyl, alkoxyalkyl, cycloalkyl, heterocycloalkyl, heterocycloalkylcarbonyl, aryl, heterocyclo, heteroaryl, cycloalkylalkyl, aryloxyalkyl, heteroaryloxyalkyl, heteroarylalkoxyalkyl, heteroarylthioalkyl, arylsulfonyl, arylalkanoyl, alkylsulfonyl, heteroarylsulfonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, alkyliminocarbonyl, aryliminocarbonyl, heterocycloiminocarbonyl, arylthioalkyl, alkylthioalkyl, arylthioalkenyl, alkylthioalkenyl, heteroarylalkyl, haloalkanoyl, hydroxyalkanoyl, thiolalkanoyl, alkenyl, alkynyl, alkoxycarbonyl, aryloxycarbonyl, aminoalkylcarbonyl, hydroxyalkyl, aminoalkyl, aminoalkylsulfonyl, and aminosulfonyl, wherein any amino of R b  and R c  is substituted with: 
 up to two substituents independently selected from the group consisting of alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl, or  
 two substituents such that the substituents, taken together with the amino nitrogen, form: 
 a saturated or partially unsaturated heterocyclo group optionally substituted with up to three substituents independently selected from the group consisting of alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl, or  
 a heteroaryl group optionally substituted with up to three independently selected R f  substituents;  
 
   each R d  and R e  is independently selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl;    each R f  is independently selected from the group consisting of nitro, hydroxy, alkyl, halogen, aryl, alkoxy, cyano, and R d R e amino;    each R g  is independently selected from the group consisting of aryl, heteroaryl, heterocyclo, aroyl, alkanoyl, heteroaroyl, halogen, cyano, aldehydo, hydroxy, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkoxy, aryloxy, heteroaryloxy, alkenyloxy, alkynyloxy, alkoxyaryl, alkoxyheteroaryl, R h R i -amino, alkoxyalkyl, alkylenedioxy, aryloxyalkyl, perfluoroalkyl, trifluoroalkyl, alkylthio, arylthio, alkoxycarbonyl, alkoxycarbonyloxy, aryloxycarbonyl, arylalkoxycarbonylamino, aryloxycarbonyloxy, carboxy, R h R i -aminocarbonyloxy, R h R i -aminocarbonyl, R h R i -aminoalkanoyl, hydroxyaminocarbonyl, R h R i -aminosulfonyl, R h R i -aminocarbonyl(R h )amino, trifluoromethylsulfonyl(R h )amino, heteroarylsulfonyl(R h )amino, arylsulfonyl(R h )amino, arylsulfonyl(R h )aminocarbonyl, alkylsulfonyl(R h )amino, arylcarbonyl(R h )aminosulfonyl, and alkylsulfonyl(R h )aminocarbonyl;    each R h  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein: 
 any such substituent is optionally substituted by up to two independently selected R j  substituents, and  
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted by up to two independently selected R j  substituents;  
   each R i  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein: 
 any such substituent is optionally substituted by up to two independently selected R j  substituents;  
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted by up to two independently selected R j  substituents;  
   each R j  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein: 
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted with up to two substituents independently selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, and alkoxycarbonyl; and  
   each R k  is independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, alkoxycarbonyl, R c R d amino carbonyl, R c R d aminosulfonyl, R c R d aminoalkanoyl, and R c R d aminoalkysulfonyl.    
     
     
         53 - 91 . (canceled).  
     
     
         92 . A process for treating a mammal having a condition associated with pathological matrix metalloprotease activity, wherein the process comprises administering a compound or salt recited in  claim 1  in an MMP enzyme-inhibiting effective amount to the mammal.  
     
     
         93 - 94 . (canceled).  
     
     
         95 . The process according to  claim 92  wherein y is one.  
     
     
         96 . The process according to  claim 92  wherein z is one.  
     
     
         97 . The process according to  claim 92  wherein the sum of y+z is zero.  
     
     
         98 . The process according to  claim 92  wherein X is —CH 2 —.  
     
     
         99 . (canceled).  
     
     
         100 . The process according to  claim 92 , wherein R 20  is —NHOH.  
     
     
         101 - 104 . (canceled).  
     
     
         105 . A process for treating a mammal having a condition associated with pathological matrix metalloprotease activity, wherein the process comprises administering a compound or salt recited in  claim 18  in an MMP enzyme-inhibiting effective amount to the mammal.  
     
     
         106 - 110 . (canceled).  
     
     
         111 . The process according to  claim 105 , wherein R 1  has a length greater than that of an octyl group and less than that of a stearyl group.  
     
     
         112 . The process according to  claim 105 , wherein R 1  is unsubstituted phenoxy or unsubstituted phenylthioxy.  
     
     
         113 . The process according to  claim 105 , wherein the compound is administered a plurality of times.  
     
     
         114 . A process for treating a mammal having a condition associated with pathological matrix metalloprotease activity, wherein: 
 the process comprises administering a compound or a pharmaceutically acceptable salt thereof in an MMP enzyme-inhibiting effective amount to the mammal;    the compound corresponds in structure to Formula VIB-2:                          as to R 5  and R 6 : 
 R 5  and R 6  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, acylalkyl, halo, nitro, hydroxyl, cyano, alkoxy, haloalkyl, haloalkoxy, hydroxyalkyl, R b R c aminoalkyl, thiol, alkylthio, arylthio, cycloalkylthio, cycloalkyloxy, alkoxyalkoxy, heterocyclooxy, and R b R c aminoalkoxy, or  
 R 5  and R 6 , together with the atoms to which they are bonded, form an aliphatic or aromatic carbocyclic or heterocyclic ring having 5- to 7-members;  
   R 7  and R 8 , taken together with the nitrogen to which they are bonded, form a -G-A-R-E-Y;    G is selected from the group consisting of piperidinyl, piperazinyl, and pyrrolidinyl;    A is selected from the group consisting of: 
 (1) —O—,  
 (2) —S—,  
 (3) —NR k —,  
 (4) —CO—N(R k )—,  
 (5) —N(R k )—CO—,  
 (6) —CO—O—,  
 (7) —O—CO—,  
 (8) —O—CO—O—,  
 (9) —HC═CH—,  
 (10) —NH—CO—NH—,  
 (11) —C≡C—,  
 (12) —N═N—,  
 (13) —NH—NH—,  
 (14) —CS—N(R k )—,  
 (15) —N(R k )—CS—,  
 (16) —CH 2 —,  
 (17) —O—CH 2 —,  
 (18) —CH 2 —O—,  
 (19) —S—CH 2 —,  
 (20) —CH 2 —S—,  
 (21) —SO—,  
 (22) —SO 2 —, and  
 (23) a bond;  
   R is selected from the group consisting of phenyl, phenylalkyl, phenyloxyalkyl, and phenylthioalkyl, wherein: 
 any phenyl portion of such substituents is optionally substituted with up to two substituents independently selected from the group consisting of halo, alkyl, perfluoroalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, amino, alkoxycarbonylalkyl, alkoxy, C 1 -C 2 -alkylenedioxy, hydroxycarbonylalkyl, hydroxycarbonylalkylamino, nitro, hydroxy, hydroxyalkyl, alkanoylamino, and alkoxycarbonyl;  
   E is selected from the group consisting of: 
 (1) —COR g —,  
 (2) —COR g ,  
 (3) —R g CO—,  
 (4) —CON(R k )—,  
 (5) —(R k )NCO—,  
 (6) —CO—,  
 (7) —SO 2 R g —,  
 (8) —SO 2 R g ,  
 (9) —R g SO 2 —,  
 (10) —SO 2 —,  
 (11) —N(R k )—SO 2 —,  
 (12) —SO 2 —N(R k )—, and  
 (13) a bond;  
   Y is absent or selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, hydroxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkyl, perfluoroalkoxy, perfluoroalkylthio, alkenyl, heterocycloalkyl, alkoxycarbonyl, and aminoalkyl, wherein: 
 the aryl, heteroaryl, or heterocycloalkyl is optionally substituted with up to two substituents independently selected from the group consisting of alkanoyl, halo, nitro, arylalkyl, aryl, alkoxy, and amino, wherein: 
 the amino is optionally substituted with up to two substituents independently selected from the group consisting of alkyl and arylalkyl;  
 
   each R b  and R c  is independently selected from the group consisting of hydrogen, alkanoyl, arylalkyl, aroyl, bisalkoxyalkyl, alkyl, haloalkyl, perfluoroalkoxyalkyl, alkoxyalkyl, cycloalkyl, heterocycloalkyl, heterocycloalkylcarbonyl, aryl, heterocyclo, heteroaryl, cycloalkylalkyl, aryloxyalkyl, heteroaryloxyalkyl, heteroarylalkoxyalkyl, heteroarylthioalkyl, arylsulfonyl, arylalkanoyl, alkylsulfonyl, heteroarylsulfonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, alkyliminocarbonyl, aryliminocarbonyl, heterocycloiminocarbonyl, arylthioalkyl, alkylthioalkyl, arylthioalkenyl, alkylthioalkenyl, heteroarylalkyl, haloalkanoyl, hydroxyalkanoyl, thiolalkanoyl, alkenyl, alkynyl, alkoxycarbonyl, aryloxycarbonyl, aminoalkylcarbonyl, hydroxyalkyl, aminoalkyl, aminoalkylsulfonyl, and aminosulfonyl, wherein any such amino is optionally substituted with: 
 up to two substituents independently selected from the group consisting of alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl, or  
 two substituents such that the two substituents, together with the amino nitrogen, form: 
 a saturated or partially unsaturated heterocyclo group optionally substituted with up to three substituents independently selected from the group consisting of alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl, or  
 a heteroaryl group optionally substituted with up to three independently selected R f  substituents;  
 
   each R d  and R e  is independently selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkyl, aryl, alkanoyl, aroyl, arylalkylcarbonyl, alkoxycarbonyl, and arylalkoxycarbonyl;    each R f  is independently selected from the group consisting of nitro, hydroxy, alkyl, halogen, aryl, alkoxy, cyano, and R d R e amino;    each R g  is independently selected from the group consisting of aryl, heteroaryl, heterocyclo, aroyl, alkanoyl, heteroaroyl, halogen, cyano, aldehydo, hydroxy, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkoxy, aryloxy, heteroaryloxy, alkenyloxy, alkynyloxy, alkoxyaryl, alkoxyheteroaryl, R h R i -amino, alkoxyalkyl, alkylenedioxy, aryloxyalkyl, perfluoroalkyl, trifluoroalkyl, alkylthio, arylthio, alkoxycarbonyl, alkoxycarbonyloxy, aryloxycarbonyl, arylalkoxycarbonyl, arylalkoxycarbonylamino, aryloxycarbonyloxy, carboxy, R h R i -aminocarbonyloxy, R h R i -aminocarbonyl, R h R i -aminoalkanoyl, hydroxyaminocarbonyl, R h R i -aminosulfonyl, R h R i aminocarbonyl(R h )amino, trifluoromethylsulfonyl(R h )amino, heteroarylsulfonyl(R h )amino, arylsulfonyl(R h )amino, arylsulfonyl(R h )aminocarbonyl, alkylsulfonyl(R h )amino, arylcarbonyl(R h )aminosulfonyl, and alkylsulfonyl(R h )aminocarbonyl substituent;    each R h  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein: 
 any such substituent is optionally substituted by up to two substituents independently selected from R j  substituents, and  
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted with up to two independently selected R j  substituents;  
   each R i  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein: 
 any such substituent is optionally substituted by up to two independently selected R j  substituents, and  
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted with up to two independently selected R j  substituents;  
   each R j  is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, alkyl, alkynyl, alkenyl, alkoxyalkyl, aminoalkyl, alkoxycarbonyl, arylalkoxycarbonyl, carboxyalkyl, haloalkyl, alkanoyl, aroyl, aminoalkanoyl, haloalkanoyl, and hydroxyalkyl, wherein: 
 the amino of the aminoalkyl or aminoalkanoyl is optionally substituted with up to two substituents independently selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, and alkoxycarbonyl; and  
   each R k  is independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxycarbonyl, alkoxycarbonyl, R c R d aminocarbonyl, R c R d aminosulfonyl, R c R d aminoalkanoyl, and R c R d aminoalkysulfonyl.    
     
     
         115 . The process according to  claim 114 , wherein the compound corresponds in structure to Formula VIB-3:  
       
         
           
           
               
               
           
         
       
     
     
         116 . The process according to  claim 114  wherein the compound corresponds in structure to Formula VIII or VIII-B  
       
         
           
           
               
               
           
         
       
     
     
         117 . The process according to  claim 114 , wherein -G-A-R-E-Y has a length greater than that of an octyl group and less than that of a stearyl group.  
     
     
         118 . (canceled).  
     
     
         119 . The process according to  claim 114  wherein the compound is administered a plurality of times.  
     
     
         120 . A process for treating a mammal having a condition associated with pathological matrix metalloprotease activity, wherein the process comprises administering a compound or salt recited in  claim 2  in an MMP enzyme-inhibiting effective amount to the mammal.  
     
     
         121 . A process for treating a mammal having a condition associated with pathological matrix metalloprotease activity, wherein the process comprises administering a compound or salt recited in  claim 12  in an MMP enzyme-inhibiting effective amount to the mammal.  
     
     
         122 . A process for treating a mammal having a condition associated with pathological matrix metalloprotease activity, wherein the process comprises administering a compound or salt recited in  claim 19  in an MMP enzyme-inhibiting effective amount to the mammal.  
     
     
         123 . A process for treating a mammal having a condition associated with pathological matrix metalloprotease activity, wherein the process comprises administering a compound or salt recited in  claim 20  in an MMP enzyme-inhibiting effective amount to the mammal.  
     
     
         124 . A process for treating a mammal having a condition associated with pathological matrix metalloprotease activity, wherein the process comprises administering a compound or salt recited in  claim 22  in an MMP enzyme-inhibiting effective amount to the mammal.