Aromatic sulfone hydroxamic acid metalloprotease inhibitor

Abstract

A treatment process is disclosed that comprises administering an effective amount of an aromatic sulfone hydroxamic acid that exhibits excellent inhibitory activity of one or more matrix metalloprotease (MMP) enzymes, such as MMP-2, MMP-9 and MMP-13, while exhibiting substantially less inhibition at least of MMP-1 to a host having a condition associated with pathological matrix metalloprotease activity. Also disclosed are metalloprotease inhibitor compounds having those selective activities, processes for manufacture of such compounds and pharmaceutical compositions using an inhibitor. A contemplated compound corresponds in structure to formula B, below,

1 - 66 . (canceled).  
     
     
         67 . A compound or a pharmaceutically acceptable salt thereof, wherein: 
 the compound corresponds in structure to the following formula:                          R 14  is selected from the group consisting of hydrogen and C(W)R 25 ;    W is selected from the group consisting of O and S;    R 25  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  
 the amino C 1 -C 6 -alkyl nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring;  
   g is zero, 1, or 2;    m is zero, 1, or 2;    n is zero, 1, or 2;    p is zero, 1, or 2;    the sum of m+n+p=1,2,3, or  4; as to X, Y, and Z:  
 (a) one of X, Y, and Z is selected from the group consisting of C(O), S, S(O), S(O) 2 , and NS(O) 2 R 7 , and the remaining two of X, Y, and Z are CR 8 R 9 , and CR 10 R 11 , or  
 (b) X and Z, or Z and Y together constitute a moiety selected from the group consisting of NR 6 C(O), NR 6 S(O), NR 6 S(O) 2 , NR 6 S, NR 60 , SS, NR 6 NR 6 , and OC(O), with the remaining one of X and Y being CR 8 R 9 , or  
 (c) n is zero and X, Y, and Z together constitute a moiety selected from the group consisting of:  
                     
   wherein wavy lines are bonds to the atoms of the depicted ring;    R 6  and R 6 ′ are independently selected from the group consisting of hydrogen, formyl, sulfonic-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxycarbonyl-C 1 -C 6 -alkyl, hydroxycarbonyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkylcarbonyl-C 1 -C 6 -alkyl, R 8 R 9 -aminocarbonyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxycarbonyl-C 1 -C 6 -alkylcarbonyl, hydroxycarbonyl-C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylcarbonyl-C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkoxycarbonylcarbonyl, hydroxycarbonylcarbonyl, C 1 -C 6 -alkylcarbonylcarbonyl, R 8 R 9 -aminocarbonylcarbonyl, C 1 -C 6 -alkanoyl, aryl-C 1 -C 6 -alkyl, aroyl, bis(C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl)-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -perfluoroalkyl, C 1 -C 6 -trifluoromethylalkyl, C 1 -C 6 -perfluoroalkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, heteroarylcarbonyl, heterocyclocarbonyl, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heterocycloalkylcarbonyl, aryl, 5- to 6-membered heterocyclo, 5- to 6-membered heteroaryl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, aryloxy-C 1 -C 6 -alkyl, heteroaryloxy-C 1 -C 6 -alkyl, heteroaryl-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, heteroarylthio-C 1 -C 6 -alkyl, arylsulfonyl, C 1 -C 6 -alkylsulfonyl, 5- to 6-membered heteroarylsulfonyl, carboxy-C 1 -C 6 -alkyl, C 1 -C 4 -alkoxycarbonyl-C 1 -C 6 -alkyl, aminocarbonyl, C 1 -C 6 -alkyl(R 8 N)iminocarbonyl, aryl(R 8 N)iminocarbonyl, 5- to 6-membered heterocyclo(R 8 N)iminocarbonyl, arylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, arylthio-C 3 -C 6 -alkenyl, C 1 -C 4 -alkylthio-C 3 -C 6 -alkenyl, 5- to 6-membered heteroaryl-C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkanoyl, hydroxy-C 1 -C 6 -alkanoyl, thiol-C 1 -C 6 -alkanoyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, C 1 -C 5 -alkoxycarbonyl, aryloxycarbonyl, NR 8 R 9 —(R 8 )iminomethyl, NR 8 R 9 —C 1 -C 5 -alkylcarbonyl, hydroxy-C 1 -C 5 -alkyl, R 8 R 9 -aminocarbonyl, R 8 R 9 -aminocarbonyl-C 1 -C 6 -alkylcarbonyl, hydroxyaminocarbonyl, R 8 R 9 -aminosulfonyl, R 8 R 9 -aminosulfon-C 1 -C 6 -alkyl, R 8 R 9 -amino-C 1 -C 6 -alkylsulfonyl, and R 8 R 9 -amino-C 1 -C 6 -alkyl;    R 7  is selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, C 1 -C 6 -alkyl, C 3 -C 6 -alkynyl, C 3 -C 6 -alkenyl, C 1 -C 6 -carboxyalkyl, and C 1 -C 6 -hydroxyalkyl;    as to R 8 : 
 R 8  is selected from the group consisting of hydrogen, hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkanoyl, aroyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, heteroaryl-C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocyclo-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, arylalkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, hydroxy-C 1 -C 6 -alkyl, hydroxycarbonyl-C 1 -C 6 -alkyl, hydroxycarbonylaryl-C 1 -C 6 -alkyl, aminocarbonyl-C 1 -C 6 -alkyl, aryloxy-C 1 -C 6 -alkyl, heteroaryloxy-C 1 -C 6 -alkyl, arylthio-C 1 -C 6 -alkyl, heteroarylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfinyl-C 1 -C 6 -alkyl, arylsulfinyl-C 1 -C 6 -alkyl, heteroarylsulfinyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfonyl-C 1 -C 6 -alkyl, arylsulfonyl-C 1 -C 6 -alkyl, heteroarylsulfonyl-C 1 -C 6 -alkyl, perfluoro-C 1 -C 6 -alkyl, trifluoromethyl-C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkyl, alkoxycarbonylamino-C 1 -C 6 -alkyl, and amino-C 1 -C 6 -alkyl, wherein: 
 the aminoalkyl nitrogen is optionally substituted with up to two substituents independently selected from the group consisting of C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkyl, cycloalkyl, and C 1 -C 6 -alkanoyl, or  
 
 R 8  and R 9 , together with the carbon to which they are bonded, form a carbonyl group, or  
 R 8  and R 9  or R 8  and R 10 , together with the atom(s) to which they are bonded, form a 5- to 8-membered carbocyclic ring, or a 5- to 8-membered heterocyclo or heteroaryl ring containing one or two heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;  
   as to R 9 : 
 R 9  is selected from the group consisting of hydrogen, hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkanoyl, aroyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, heteroaryl-C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocyclo-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, arylalkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, hydroxy-C 1 -C 6 -alkyl, hydroxycarbonyl-C 1 -C 6 -alkyl, hydroxycarbonylaryl-C 1 -C 6 -alkyl, aminocarbonyl-C 1 -C 6 -alkyl, aryloxy-C 1 -C 6 -alkyl, heteroaryloxy-C 1 -C 6 -alkyl, arylthio-C 1 -C 6 -alkyl, heteroarylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfinyl-C 1 -C 6 -alkyl, arylsulfinyl-C 1 -C 6 -alkyl, heteroarylsulfinyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfonyl-C 1 -C 6 -alkyl, arylsulfonyl-C 1 -C 6 -alkyl, heteroarylsulfonyl-C 1 -C 6 -alkyl, perfluoro-C 1 -C 6 -alkyl, trifluoromethyl-C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkyl, alkoxycarbonylamino-C 1 -C 6 -alkyl, and amino-C 1 -C 6 -alkyl, wherein: 
 the aminoalkyl nitrogen is optionally substituted with up to two substituents independently selected from the group consisting of C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkyl, cycloalkyl, and C 1 -C 6 -alkanoyl, or  
 
 R 8  and R 9 , together with the carbon to which they are bonded, form a carbonyl group, a 5- to 8-membered carbocyclic ring, or a 5- to 8-membered heterocyclo or heteroaryl ring containing one or two heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;  
   as to R 10 : 
 R 10  is selected from the group consisting of hydrogen, hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkanoyl, aroyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, heteroaryl-C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocyclo-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, arylalkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, hydroxy-C 1 -C 6 -alkyl, hydroxycarbonyl-C 1 -C 6 -alkyl, hydroxycarbonylaryl-C 1 -C 6 -alkyl, aminocarbonyl-C 1 -C 6 -alkyl, aryloxy-C 1 -C 6 -alkyl, heteroaryloxy-C 1 -C 6 -alkyl, arylthio-C 1 -C 6 -alkyl, heteroarylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfinyl-C 1 -C 6 -alkyl, arylsulfinyl-C 1 -C 6 -alkyl, heteroarylsulfinyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfonyl-C 1 -C 6 -alkyl, arylsulfonyl-C 1 -C 6 -alkyl, heteroarylsulfonyl-C 1 -C 6 -alkyl, perfluoro-C 1 -C 6 -alkyl, trifluoromethyl-C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkyl, alkoxycarbonylamino-C 1 -C 6 -alkyl, and amino-C 1 -C 6 -alkyl, wherein: 
 the aminoalkyl nitrogen is optionally substituted with up to two substituents independently selected from the group consisting of C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkyl, cycloalkyl, and C 1 -C 6 -alkanoyl,  
 
 R 10  and R 11 , together with the carbon to which they are bonded, form a carbonyl group, or  
 R 10  and R 11  or R 8  and R 10 , together with the atom(s) to which they are bonded, form a 5- to 8-membered carbocyclic ring, or a 5- to 8-membered heterocyclo or heteroaryl ring containing one or two heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;  
   as to R 11 : 
 R 11  is selected from the group consisting of hydrogen, hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkanoyl, aroyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, heteroaryl-C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocyclo-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, arylalkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, hydroxy-C 1 -C 6 -alkyl, hydroxycarbonyl-C 1 -C 6 -alkyl, hydroxycarbonylaryl-C 1 -C 6 -alkyl, aminocarbonyl-C 1 -C 6 -alkyl, aryloxy-C 1 -C 6 -alkyl, heteroaryloxy-C 1 -C 6 -alkyl, arylthio-C 1 -C 6 -alkyl, heteroarylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfinyl-C 1 -C 6 -alkyl, arylsulfinyl-C 1 -C 6 -alkyl, heteroarylsulfinyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfonyl-C 1 -C 6 -alkyl, arylsulfonyl-C 1 -C 6 -alkyl, heteroarylsulfonyl-C 1 -C 6 -alkyl, perfluoro-C 1 -C 6 -alkyl, trifluoromethyl-C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkyl, alkoxycarbonylamino-C 1 -C 6 -alkyl, and amino-C 1 -C 6 -alkyl, wherein: 
 the aminoalkyl nitrogen is optionally substituted with up to two substituents independently selected from the group consisting of C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkyl, cycloalkyl, and C 1 -C 6 -alkanoyl, or  
 
 R 10  and R 11 , together with the carbon to which they are bonded, form a carbonyl group, a 5- to 8-membered carbocyclic ring, or a 5- to 8-membered heterocyclo or heteroaryl ring containing one or two heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;  
   only one of R 8  and R 9  or R 10  and R 11  is hydroxy;    R 12  and R 12 ′ are independently selected from the group consisting of hydrogen, C 1 -C 6 -alkyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, heteroarylalkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocyclo-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, aryloxy-C 1 -C 6 -alkyl, amino-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, hydroxy-C 1 -C 6 -alkyl, hydroxycarbonyl-C 1 -C 6 -alkyl, hydroxycarbonylaryl-C 1 -C 6 -alkyl, aminocarbonyl-C 1 -C 6 -alkyl, aryloxy-C 1 -C 6 -alkyl, heteroaryloxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, arylthio-C 1 -C 6 -alkyl, heteroarylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfinyl-C 1 -C 6 -alkyl, arylsulfinyl-C 1 -C 6 -alkyl, heteroarylsulfinyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfonyl-C 1 -C 6 -alkyl, arylsulfonyl-C 1 -C 6 -alkyl, heteroarylsulfonyl-C 1 -C 6 -alkyl, perfluoro-C 1 -C 6 -alkyl, trifluoromethyl-C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkyl, alkoxycarbonylamino-C 1 -C 6 -alkyl, and amino-C 1 -C 6 -alkyl, wherein: 
 the aminoalkyl nitrogen is optionally substituted with up to two substituents independently selected from the group consisting of C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkyl, cycloalkyl, and C 1 -C 6 -alkanoyl;  
   R 13  is selected from the group consisting of hydrogen, benzyl, phenyl, C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, and C 1 -C 6 -hydroxyalkyl;    Q is a 5- to 7-membered heterocyclic ring (other than piperazinyl) containing one or two nitrogen atoms;    A is selected from the group consisting of: 
 (1)—O—,  
 (2) —S—,  
 (3) —NR 17 —,  
 (4) —CO—N(R 17 ),  
 (5) —N(R 17 )—CO—,  
 (6) —CO—O—,  
 (7) —O—CO—,  
 (8) —O—CO—O—,  
 (9) —HC═CH—,  
 (10) —NH—CO—NH—,  
 (11) —C≡C—,  
 (12)—NH—CO—O—,  
 (13) —O—CO—NH—,  
 (14) —N═N—,  
 (15) —NH—NH—,  
 (16) —CS—N(R 17 )—,  
 (17) —N(R 17 )—CS—, and  
 (18) a bond;  
   R 17  is selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, and phenyl;    R is selected from the group consisting of alkyl, alkoxyalkyl, aryl, heteroaryl, cycloalkyl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl, cycloalkylalkyl, cycloalkyloxyalkyl, heterocycloalkoxyalkyl, aryloxyalkyl, heteroaryloxyalkyl, arylthioalkyl, heteroarylthioalkyl, cycloalkylthioalkyl, and heterocyclothioalkyl, wherein: 
 the aryl, heteroaryl, cycloalkyl, or heterocyclo 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 -alkylene-dioxy, hydroxycarbonylalkyl, hydroxycarbonylalkylamino, nitro, hydroxy, hydroxyalkyl, alkanoylamino, and alkoxycarbonyl;  
   R is other than alkyl or alkoxyalkyl when A is —O— or —S—;    E is selected from the group consisting of: 
 (1) —CO(R 19 )—,  
 (2) —(R 19 )CO—,  
 (3) —CONH—,  
 (4) —HNCO—,  
 (5) —CO—,  
 (6) —SO 2 —R 19 —,  
 (7) —R 19 —SO 2 —,  
 (8) —SO 2 —,  
 (9)—NH—SO 2 —,  
 (10) —SO 2 —NH—,  
 (11) —S—,  
 (12) —NH—CO—O—,  
 (13) —O—CO—NH—, and  
 (14) a bond;  
   R 19  is selected from the group consisting of heterocycloalkyl and cycloalkyl; and    Y 2  is selected from the group consisting of hydrogen, alkyl, alkoxy, haloalkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, hydroxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, alkenyl, heterocycloalkyl, trifluoromethyl, alkoxycarbonyl, and aminoalkyl, wherein: 
 the aryl, heteroaryl, aralkyl, or heterocycloalkyl is optionally substituted with up to two substituents independently selected from the group consisting of alkanoyl, halo, nitro, arylalkyl, aryl, alkoxy, trifluoroalkyl, trifluoroalkoxy, and amino, wherein: 
 the amino nitrogen is optionally substituted with up to two substituents independently selected from the group consisting of alkyl and arylalkyl.  
 
   
     
     
         68 . A compound or salt according to  claim 67 , wherein g is 2.  
     
     
         69 . A compound or salt according to  claim 68 , wherein A-R-E-Y 2  is bonded at the 4-position of Q relative to the phenyl-bonded nitrogen of Q when Q is a 6- or 7-membered ring, and at the 3- or 4-position of Q relative to the phenyl-bonded nitrogen of Q when Q is a 5-membered ring.  
     
     
         70 . A compound or salt according to  claim 69 , wherein R 14  is hydrogen.  
     
     
         71 . A compound or salt according to  claim 69 , wherein: 
 R 14  is C(W)R 25 ;    W is O; and    R 25  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, and aryloxy.    
     
     
         72 . A compound or salt according to  claim 69 , wherein A is selected from the group consisting of —O— and —S—.  
     
     
         73 . A compound or salt according to  claim 69 , wherein R is selected from the group consisting of aryl, heteroaryl, cycloalkyl, and heterocyclo.  
     
     
         74 . A compound or salt according to  claim 69 , wherein the compound corresponds in structure to formula B-1A:  
       
         
           
           
               
               
           
         
       
     
     
         75 . A compound or salt according to  claim 69 , wherein Q is a 5-membered ring.  
     
     
         76 . A compound or salt according to  claim 69 , wherein Q is a 7-membered ring.  
     
     
         77 . A compound or salt according to  claim 69 , wherein Q is a 6-membered ring.  
     
     
         78 . A compound or salt according to  claim 77 , wherein the compound corresponds in structure to the following formula:  
       
         
           
           
               
               
           
         
       
     
     
         79 . A compound or salt according to  claim 78 , wherein: 
 the compound corresponds in structure to the following formula:                          Z is selected from the group consisting of C(O), S, S(O), S(O) 2 , and NS(O) 2 R 7 .    
     
     
         80 . A compound or salt according to  claim 79 , wherein R is selected from the group consisting of alkyl, alkoxyalkyl, aryl, heteroaryl, cycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkyl, cycloalkylalkyl, heterocycloalkoxyalkyl, aryloxyalkyl, heteroaryloxyalkyl, arylthioalkyl, heteroarylthioalkyl, and cycloalkylthioalkyl, wherein: 
 the aryl, heteroaryl, or cycloalkyl 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 -alkylene-dioxy, hydroxycarbonylalkyl, hydroxycarbonylalkylamino, nitro, hydroxy, hydroxyalkyl, alkanoylamino, and alkoxycarbonyl.    
     
     
         81 . A compound or salt according to  claim 80 , wherein R is selected from the group consisting of aryl, heteroaryl, and cycloalkyl.  
     
     
         82 . A compound or salt according to  claim 79 , wherein Z is S.  
     
     
         83 . A compound or salt according to  claim 68 , wherein the compound corresponds in structure to the formula:  
       
         
           
           
               
               
           
         
       
     
     
         84 . A compound or salt according to  claim 83 , wherein R-E-Y 2  is bonded at the 4-position of Q relative to the phenyl-bonded nitrogen of Q when Q is a 6- or 7-membered ring, and at the 3- or 4-position of Q relative to the phenyl-bonded nitrogen of Q when Q is a 5-membered ring.  
     
     
         85 . A compound or salt according to  claim 84 , wherein: 
 the compound corresponds in structure to formula XI-1:                          Z is selected from the group consisting of C(O), S, S(O), S(O) 2 , and NS(O) 2 R 7 .    
     
     
         86 . A compound or a pharmaceutically acceptable salt thereof, wherein: 
 the compound corresponds in structure to the following formula:                          R 14  is selected from the group consisting of hydrogen and C(W)R 25 ;    W is selected from the group consisting of O and S;    R 25  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  
 the amino C 1 -C 6 -alkyl nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring;  
   g is zero, 1, or 2;    m is zero, 1, or 2;    n is zero, 1, or 2;    p is zero, 1, or 2;    the sum of m+n+p=1, 2, 3, or 4;    as to X, Y, and Z: 
 (a) one of X, Y, and Z is selected from the group consisting of C(O), S, S(O), S(O) 2 , and NS(O) 2 R 7 , and the remaining two of X, Y, and Z are CR 8 R 9 , and CR 10 R 11 , or  
 (b) X and Z, or Z and Y together constitute a moiety selected from the group consisting of NR 6 C(O), NR 6 S(O), NR 6 S(O) 2 , NR 6 S, NR 60 , SS, NR 6 NR 6 , and OC(O), with the remaining one of X and Y being CR 8 R 9 , or  
 (c) n is zero and X, Y, and Z together constitute a moiety selected from the group consisting of:  
                     
   wherein wavy lines are bonds to the atoms of the depicted ring;    R 6  and R 6  are independently selected from the group consisting of hydrogen, formyl, sulfonic-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxycarbonyl-C 1 -C 6 -alkyl, hydroxycarbonyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkylcarbonyl-C 1 -C 6 -alkyl, R 8 R 9 -aminocarbonyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxycarbonyl-C 1 -C 6 -alkylcarbonyl, hydroxycarbonyl-C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylcarbonyl-C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkoxycarbonylcarbonyl, hydroxycarbonylcarbonyl, C 1 -C 6 -alkylcarbonylcarbonyl, R 8 R 9 -aminocarbonylcarbonyl, C 1 -C 6 -alkanoyl, aryl-C 1 -C 6 -alkyl, aroyl, bis(C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl)-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -perfluoroalkyl, C 1 -C 6 -trifluoromethylalkyl, C 1 -C 6 -perfluoroalkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, heteroarylcarbonyl, heterocyclocarbonyl, 3- to 8-membered heterocycloalkyl, 3- to 8-membered heterocycloalkylcarbonyl, aryl, 5- to 6-membered heterocyclo, 5- to 6-membered heteroaryl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, aryloxy-C 1 -C 6 -alkyl, heteroaryloxy-C 1 -C 6 -alkyl, heteroaryl-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, heteroarylthio-C 1 -C 6 -alkyl, arylsulfonyl, C 1 -C 6 -alkylsulfonyl, 5- to 6-membered heteroarylsulfonyl, carboxy-C 1 -C 6 -alkyl, C 1 -C 4 -alkoxycarbonyl-C 1 -C 6 -alkyl, aminocarbonyl, C 1 -C 6 -alkyl(R 8 N)iminocarbonyl, aryl(R 8 N)iminocarbonyl, 5- to 6-membered heterocyclo(R 8 N)iminocarbonyl, arylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, arylthio-C 3 -C 6 -alkenyl, C 1 -C 4 -alkylthio-C 3 -C 6 -alkenyl, 5- to 6-membered heteroaryl-C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkanoyl, hydroxy-C 1 -C 6 -alkanoyl, thiol-C 1 -C 6 -alkanoyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, C 1 -C 5 -alkoxycarbonyl, aryloxycarbonyl, NR 8 R 9 —(R 8 )iminomethyl, NR 8 R 9 —C 1 -C 5 -alkylcarbonyl, hydroxy-C 1 -C 5 -alkyl, R 8 R 9 -aminocarbonyl, R 8 R 9 -aminocarbonyl-C 1 -C 6 -alkylcarbonyl, hydroxyaminocarbonyl, R 8 R 9 -aminosulfonyl, R 8 R 9 -aminosulfon-C 1 -C 6 -alkyl, R 8 R 9 -amino-C 1 -C 6 -alkylsulfonyl, and R 8 R 9 -amino-C 1 -C 6 -alkyl;    R 7  is selected from the group consisting of arylalkyl, aryl, heteroaryl, heterocyclo, C 1 -C 6 -alkyl, C 3 -C 6 -alkynyl, C 3 -C 6 -alkenyl, C 1 -C 6 -carboxyalkyl, and C 1 -C 6 -hydroxyalkyl;    as to R 8 : 
 R 8  is selected from the group consisting of hydrogen, hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkanoyl, aroyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, heteroaryl-C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocyclo-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, arylalkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, hydroxy-C 1 -C 6 -alkyl, hydroxycarbonyl-C 1 -C 6 -alkyl, hydroxycarbonylaryl-C 1 -C 6 -alkyl, aminocarbonyl-C 1 -C 6 -alkyl, aryloxy-C 1 -C 6 -alkyl, heteroaryloxy-C 1 -C 6 -alkyl, arylthio-C 1 -C 6 -alkyl, heteroarylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfinyl-C 1 -C 6 -alkyl, arylsulfinyl-C 1 -C 6 -alkyl, heteroarylsulfinyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfonyl-C 1 -C 6 -alkyl, arylsulfonyl-C 1 -C 6 -alkyl, heteroarylsulfonyl-C 1 -C 6 -alkyl, perfluoro-C 1 -C 6 -alkyl, trifluoromethyl-C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkyl, alkoxycarbonylamino-C 1 -C 6 -alkyl, and amino-C 1 -C 6 -alkyl, wherein: 
 the aminoalkyl nitrogen is optionally substituted with up to two substituents independently selected from the group consisting of C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkyl, cycloalkyl, and C 1 -C 6 -alkanoyl, or  
 
 R 8  and R 9 , together with the carbon to which they are bonded, form a carbonyl group, or  
 R 8  and R 9  or R 8  and R 10 , together with the atom(s) to which they are bonded, form a 5- to 8-membered carbocyclic ring, or a 5- to 8-membered heterocyclo or heteroaryl ring containing one or two heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;  
   as to R 9 : 
 R 9  is selected from the group consisting of hydrogen, hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkanoyl, aroyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, heteroaryl-C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol -C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocyclo-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, arylalkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, hydroxy-C 1 -C 6 -alkyl, hydroxycarbonyl-C 1 -C 6 -alkyl, hydroxycarbonylaryl-C 1 -C 6 -alkyl, aminocarbonyl-C 1 -C 6 -alkyl, aryloxy-C 1 -C 6 -alkyl, heteroaryloxy-C 1 -C 6 -alkyl, arylthio-C 1 -C 6 -alkyl, heteroarylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfinyl-C 1 -C 6 -alkyl, arylsulfinyl-C 1 -C 6 -alkyl, heteroarylsulfinyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfonyl-C 1 -C 6 -alkyl, arylsulfonyl-C 1 -C 6 -alkyl, heteroarylsulfonyl-C 1 -C 6 -alkyl, perfluoro-C 1 -C 6 -alkyl, trifluoromethyl-C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkyl, alkoxycarbonylamino-C 1 -C 6 -alkyl, and amino-C 1 -C 6 -alkyl, wherein: 
 the aminoalkyl nitrogen is optionally substituted with up to two substituents independently selected from the group consisting of C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkyl, cycloalkyl, and C 1 -C 6 -alkanoyl, or  
 
 R 8  and R 9 , together with the carbon to which they are bonded, form a carbonyl group, a 5- to 8-membered carbocyclic ring, or a 5- to 8-membered heterocyclo or heteroaryl ring containing one or two heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;  
   as to R 10 : 
 R 10  is selected from the group consisting of hydrogen, hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkanoyl, aroyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, heteroaryl-C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocyclo-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, arylalkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, hydroxy-C 1 -C 6 -alkyl, hydroxycarbonyl-C 1 -C 6 -alkyl, hydroxycarbonylaryl-C 1 -C 6 -alkyl, aminocarbonyl-C 1 -C 6 -alkyl, aryloxy-C 1 -C 6 -alkyl, heteroaryloxy-C 1 -C 6 -alkyl, arylthio-C 1 -C 6 -alkyl, heteroarylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfinyl-C 1 -C 6 -alkyl, arylsulfinyl-C 1 -C 6 -alkyl, heteroarylsulfinyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfonyl-C 1 -C 6 -alkyl, arylsulfonyl-C 1 -C 6 -alkyl, heteroarylsulfonyl-C 1 -C 6 -alkyl, perfluoro-C 1 -C 6 -alkyl, trifluoromethyl-C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkyl, alkoxycarbonylamino-C 1 -C 6 -alkyl, and amino-C 1 -C 6 -alkyl, wherein: 
 the aminoalkyl nitrogen is optionally substituted with up to two substituents independently selected from the group consisting of C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkyl, cycloalkyl, and C 1 -C 6 -alkanoyl,  
 
 R 10  and R 11 , together with the carbon to which they are bonded, form a carbonyl group, or  
 R 10  and R 11  or R 8  and R 10 , together with the atom(s) to which they are bonded, form a 5- to 8-membered carbocyclic ring, or a 5- to 8-membered heterocyclo or heteroaryl ring containing one or two heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;  
   as to R 11 : 
 R 11  is selected from the group consisting of hydrogen, hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkanoyl, aroyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, heteroaryl-C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocyclo-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, arylalkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, hydroxy-C 1 -C 6 -alkyl, hydroxycarbonyl-C 1 -C 6 -alkyl, hydroxycarbonylaryl-C 1 -C 6 -alkyl, aminocarbonyl-C 1 -C 6 -alkyl, aryloxy-C 1 -C 6 -alkyl, heteroaryloxy-C 1 -C 6 -alkyl, arylthio-C 1 -C 6 -alkyl, heteroarylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfinyl-C 1 -C 6 -alkyl, arylsulfinyl-C 1 -C 6 -alkyl, heteroarylsulfinyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfonyl-C 1 -C 6 -alkyl, arylsulfonyl-C 1 -C 6 -alkyl, heteroarylsulfonyl-C 1 -C 6 -alkyl, perfluoro-C 1 -C 6 -alkyl, trifluoromethyl-C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkyl, alkoxycarbonylamino-C 1 -C 6 -alkyl, and amino-C 1 -C 6 -alkyl, wherein: 
 the aminoalkyl nitrogen is optionally substituted with up to two substituents independently selected from the group consisting of C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkyl, cycloalkyl, and C 1 -C 6 -alkanoyl, or  
 
 R 10  and R 11 , together with the carbon to which they are bonded, form a carbonyl group, a 5- to 8-membered carbocyclic ring, or a 5- to 8-membered heterocyclo or heteroaryl ring containing one or two heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;  
   only one of R 8  and R 9  or R 10  and R 11  is hydroxy;    R 12  and R 12  are independently selected from the group consisting of hydrogen, C 1 -C 6 -alkyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, heteroarylalkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocyclo-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, aryloxy-C 1 -C 6 -alkyl, amino-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, hydroxy-C 1 -C 6 -alkyl, hydroxycarbonyl-C 1 -C 6 -alkyl, hydroxycarbonylaryl-C 1 -C 6 -alkyl, aminocarbonyl-C 1 -C 6 -alkyl, aryloxy-C 1 -C 6 -alkyl, heteroaryloxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, arylthio-C 1 -C 6 -alkyl, heteroarylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfinyl-C 1 -C 6 -alkyl, arylsulfinyl-C 1 -C 6 -alkyl, heteroarylsulfinyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfonyl-C 1 -C 6 -alkyl, arylsulfonyl-C 1 -C 6 -alkyl, heteroarylsulfonyl-C 1 -C 6 -alkyl, perfluoro-C 1 -C 6 -alkyl, trifluoromethyl-C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkyl, alkoxycarbonylamino-C 1 -C 6 -alkyl, and amino-C 1 -C 6 -alkyl, wherein: 
 the aminoalkyl nitrogen is optionally substituted with up to two substituents independently selected from the group consisting of C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkyl, cycloalkyl, and C 1 -C 6 -alkanoyl;  
   R 13  is selected from the group consisting of hydrogen, benzyl, phenyl, C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, and C 1 -C 6 -hydroxyalkyl;    Q is a 5- to 7-membered heterocyclic ring (other than piperazinyl) containing one or two nitrogen atoms;    E is selected from the group consisting of: 
 (1) —CO(R 19 )—,  
 (2) —(R 19 )CO—,  
 (3) —CONH—,  
 (4) —HNCO—,  
 (5) —CO—,  
 (6) —SO 2 —R 19 —,  
 (7) —R 19 —SO 2 —,  
 (8) —SO 2 —,  
 (9) —NH—SO 2 —,  
 (10) —SO 2 —NH—,  
 (11) —S—,  
 (12) —NH—CO—O—,  
 (13) —O—CO—NH—, and  
 (14) a bond;  
   R 19  is selected from the group consisting of heterocycloalkyl and cycloalkyl; and    Y 2  is selected from the group consisting of alkyl, alkoxy, haloalkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, hydroxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, alkenyl, heterocyclo, heterocycloalkyl, trifluoromethyl, alkoxycarbonyl, and aminoalkyl, wherein: 
 the aryl, heteroaryl, aralkyl, heterocyclo, or heterocycloalkyl is optionally substituted with up to two substituents independently selected from the group consisting of alkyl, alkanoyl, halo, nitro, arylalkyl, aryl, alkoxy, trifluoroalkyl, trifluoroalkoxy, and amino, wherein: 
 the amino nitrogen is optionally substituted with up to two substituents independently selected from the group consisting of alkyl and arylalkyl.  
 
   
     
     
         87 . A compound or salt according to  claim 86 , wherein g is 2.  
     
     
         88 . A compound or salt according to  claim 87 , wherein the compound corresponds in structure to the following formula:  
       
         
           
           
               
               
           
         
       
     
     
         89 . A compound or salt according to  claim 87 , wherein: 
 the compound corresponds in structure to formula IX-2:                          Z is selected from the group consisting of C(O), S, S(O), S(O) 2 , and NS(O) 2 R 7 .    
     
     
         90 . A compound or salt according to  claim 87 , wherein E-Y 2  is bonded at the 4-position of Q relative to the phenyl-bonded nitrogen of Q when Q is a 6- or 7-membered ring, and at the 3- or 4-position of Q relative to the phenyl-bonded nitrogen of Q when Q is a 5-membered ring.  
     
     
         91 . A compound or salt according to  claim 90 , wherein Y 2  is selected from the group consisting of alkyl, alkoxy, haloalkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, hydroxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, alkenyl, heterocycloalkyl, trifluoromethyl, alkoxycarbonyl, and aminoalkyl, wherein: 
 the aryl, heteroaryl, aralkyl, or heterocycloalkyl is optionally substituted with up to two substituents independently selected from the group consisting of alkanoyl, halo, nitro, arylalkyl, aryl, alkoxy, trifluoroalkyl, trifluoroalkoxy, and amino, wherein: 
 the amino nitrogen is optionally substituted with up to two substituents independently selected from the group consisting of alkyl and arylalkyl.  
   
     
     
         92 . A compound or salt according to  claim 90 , wherein R 14  is hydrogen.  
     
     
         93 . A compound or salt according to  claim 90 , wherein: 
 R 14  is C(W)R 25 ;    W is O; and    R 25  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 -Cs-cycloalkyl-C 1 -C 6 -alkyl, and aryloxy.    
     
     
         94 . A compound or salt according to  claim 90 , wherein the compound corresponds in structure to formula B-3A:  
       
         
           
           
               
               
           
         
       
     
     
         95 . A compound or salt according to  claim 90 , wherein Q is a 5-membered ring.  
     
     
         96 . A compound or salt according to  claim 90 , wherein Q is a 7-membered ring.  
     
     
         97 . A compound or salt according to  claim 90 , wherein Q is a 6-membered ring.  
     
     
         98 . A compound or salt according to  claim 97 , wherein the compound corresponds in structure to the following formula:  
       
         
           
           
               
               
           
         
       
     
     
         99 . A compound or salt according to  claim 98 , wherein: 
 the compound corresponds in structure to formula IX-1:                          Z is selected from the group consisting of C(O), S, S(O), S(O) 2 , and NS(O) 2 R 7 .    
     
     
         100 . A compound or salt according to  claim 99 , wherein Y 2  is selected from the group consisting of alkyl, alkoxy, haloalkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, hydroxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, alkenyl, heterocycloalkyl, trifluoromethyl, alkoxycarbonyl, and aminoalkyl, wherein: 
 the aryl, heteroaryl, aralkyl, or heterocycloalkyl is optionally substituted with up to two substituents independently selected from the group consisting of alkanoyl, halo, nitro, arylalkyl, aryl, alkoxy, trifluoroalkyl, trifluoroalkoxy, and amino, wherein:    the amino nitrogen is optionally substituted with up to two substituents independently selected from the group consisting of alkyl and arylalkyl.    
     
     
         101 . A compound or salt according to  claim 99 , wherein Z is S.  
     
     
         102 . A compound or salt according to  claim 101 , wherein the compound corresponds in structure to the formula:  
       
         
           
           
               
               
           
         
       
     
     
         103 . A method for treating a pathological condition in a mammal, wherein: 
 the condition is treatable by inhibiting matrix metalloprotease activity;    the method comprises administering a compound or a pharmaceutically acceptable salt thereof to the mammal in an amount that is effective to treat the condition;    the compound corresponds in structure to a compound recited in  claim 68;  and    the compound or salt inhibits the activity of one or more of MMP-2, MMP-9, and MMP-13, while exhibiting substantially less inhibitory activity against MMP-1.    
     
     
         104 . A method according to  claim 103 , wherein A is a bond.  
     
     
         105 . A method according to  claim 103 , wherein the pathological condition is selected from the group consisting of rheumatoid arthritis, osteoarthritis, septic arthritis, corneal, epidermal or gastric ulceration, tumor metastasis, invasion or angiogenesis, periodontal disease, proteinuria, Alzheimer's disease, coronary thrombosis, and bone disease.  
     
     
         106 . A method according to  claim 105 , wherein the pathological condition is osteoarthritis.  
     
     
         107 . A method according to  claim 103 , wherein the compound or salt is administered a plurality of times.  
     
     
         108 . A method for treating a pathological condition in a mammal, wherein: 
 the condition is treatable by inhibiting matrix metalloprotease activity;    the method comprises administering a compound or a pharmaceutically acceptable salt thereof to the mammal in an amount that is effective to treat the condition;    the compound corresponds in structure to a compound recited in  claim 87;  and    the compound or salt inhibits the activity of one or more of MMP-2, MMP-9, and MMP-13, while exhibiting substantially less inhibitory activity against MMP-1.    
     
     
         109 . A method according to  claim 108 , wherein the pathological condition is selected from the group consisting of rheumatoid arthritis, osteoarthritis, septic arthritis, corneal, epidermal or gastric ulceration, tumor metastasis, invasion or angiogenesis, periodontal disease, proteinuria, Alzheimer's disease, coronary thrombosis, and bone disease.  
     
     
         110 . A method according to  claim 109 , wherein the pathological condition is osteoarthritis.  
     
     
         111 . A method according to  claim 108 , wherein the compound or salt is administered a plurality of times.  
     
     
         112 . A pharmaceutical composition that comprises a compound or salt according to  claim 68  dissolved or dispersed in a pharmaceutically acceptable carrier.  
     
     
         113 . A pharmaceutical composition according to  claim 112 , wherein A is a bond.  
     
     
         114 . A pharmaceutical composition that comprises a compound or salt according to  claim 87  dissolved or dispersed in a pharmaceutically acceptable carrier.