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.

What is claimed:  
     
         1 . A process for treating a host mammal having a condition associated with pathological matrix metalloprotease (MMP) activity that comprises administering a metalloprotease inhibitor compound or a pharmaceutically acceptable salt thereof in an effective amount to a mammalian host having such a condition, said metalloprotease inhibitor inhibiting the activity of one or more of MMP-2, MMP-9 and MMP-13, while exhibiting substantially less inhibitory activity against MMP-1, said compound corresponding in structure to formula (I), below  
       
         
           
           
               
               
           
         
         wherein  
         R 1  and R 2  are both hydrido or R 1  and R 2  together with the atoms to which they are bonded form a 5- to 8-membered ring containing one, two or three heteroatoms in the ring that are oxygen, sulfur or nitrogen;  
         R 3  is an optionally substituted aryl or optionally substituted heteroaryl radical, and when said aryl or heteroaryl radical is substituted, the substituent is (a) selected from the group consisting of an optionally substituted cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, aralkoxy, heteroaralkoxy, aralkoxyalkyl, aryloxyalkyl, aralkanoylalkyl, arylcarbonylalkyl, aralkylaryl, aryloxyalkylaryl, aralkoxyaryl, arylazoaryl, arylhydrazinoaryl, alkylthioaryl, arylthioalkyl, alkylthioaralkyl, aralkylthioalkyl, an aralkylthioaryl radical, the sulfoxide or sulfone of any of the thio substituents, and a fused ring structure comprising two or more 5-or 6-membered rings selected from the group consisting of aryl, heteroaryl, cycloalkyl and heterocycloalkyl, and (b) is itself optionally substituted with one or more substituents independently selected from the group consisting of a cyano, perfluoroalkyl, trifluoromethoxy, trifluoromethylthio, haloalkyl, trifluoromethylalkyl, aralkoxycarbonyl, aryloxycarbonyl, hydroxy, halo, alkyl, alkoxy, nitro, thiol, hydroxycarbonyl, aryloxy, arylthio, aralkyl, aryl, arylcarbonylamino, heteroaryloxy, heteroarylthio, heteroaralkyl, cycloalkyl, heterocyclooxy, heterocyclothio, heterocycloamino, cycloalkyloxy, cycloalkylthio, heteroaralkoxy, heteroaralkylthio, aralkoxy, aralkylthio, aralkylamino, heterocyclo, heteroaryl, arylazo, hydroxycarbonylalkoxy, alkoxycarbonylalkoxy, alkanoyl, arylcarbonyl, aralkanoyl, alkanoyloxy, aralkanoyloxy, hydroxyalkyl, hydroxyalkoxy, alkylthio, alkoxyalkylthio, alkoxycarbonyl, aryloxyalkoxyaryl, arylthioalkylthioaryl, aryloxyalkylthioaryl, arylthioalkoxyaryl, hydroxycarbonylalkoxy, hydroxycarbonylalkylthio, alkoxycarbonylalkoxy, alkoxycarbonylalkylthio, amino, 
 wherein the amino nitrogen is (i) unsubstituted, or (ii) substituted with one or two substituents that are independently selected from the group consisting of an alkyl, aryl, heteroaryl, aralkyl, cycloalkyl, aralkoxycarbonyl, alkoxycarbonyl, arylcarbonyl, aralkanoyl, heteroarylcarbonyl, heteroaralkanoyl and an alkanoyl group, or (iii) wherein the amino nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring containing zero to two additional heteroatoms that are nitrogen, oxygen or sulfur and which ring itself is (a) unsubstituted or (b) substituted with one or two groups independently selected from the group consisting of an aryl, alkyl, heteroaryl, aralkyl, heteroaralkyl, hydroxy, alkoxy, alkanoyl, cycloalkyl, heterocycloalkyl, alkoxycarbonyl, hydroxyalkyl, trifluoromethyl, benzofused heterocycloalkyl, hydroxyalkoxyalkyl, aralkoxycarbonyl, hydroxycarbonyl, aryloxycarbonyl, benzofused heterocycloalkoxy, benzofused cycloalkylcarbonyl, heterocycloalkylcarbonyl, and a cycloalkylcarbonyl group, carbonylamino  
 wherein the carbonylamino nitrogen is (i) unsubstituted, or (ii) is the reacted amine of an amino acid, or (iii) substituted with one or two radicals selected from the group consisting of an alkyl, hydroxyalkyl, hydroxyheteroaralkyl, cycloalkyl, aralkyl, trifluoromethylalkyl, heterocycloalkyl, benzofused heterocycloalkyl, benzofused heterocycloalkyl, benzofused cycloalkyl, and an N,N-dialkylsubstituted alkylamino-alkyl group, or (iv) the carboxamido nitrogen and two substituents bonded thereto together form a 5- to 8-membered heterocyclo, heteroaryl or benzofused heterocycloalkyl ring that is itself unsubstituted or substituted with one or two radicals independently selected from the group consisting of an alkyl, alkoxycarbonyl, nitro, heterocycloalkyl, hydroxy, hydroxycarbonyl, aryl, aralkyl, heteroaralkyl and an amino group, 
 wherein the amino nitrogen is (i) unsubstituted, or (ii) substituted with one or two substituents that are independently selected from the group consisting of alkyl, aryl, and heteroaryl, or (iii) wherein the amino nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring,  
 and an aminoalkyl group  
 
 
         wherein the aminoalkyl nitrogen is (i) unsubstituted, or (ii) substituted with one or two substituents independently selected from the group consisting of an alkyl, aryl, aralkyl, cycloalkyl, aralkoxycarbonyl, alkoxycarbonyl, and an alkanoyl group, or (iii) wherein the aminoalkyl nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring.  
       
     
     
         2 . The process according to    claim 1    wherein R 1  and R 2  together with the atoms to which they are bonded form a 5- to 8-membered ring containing one, two or three heteroatoms in the ring that are oxygen, sulfur or nitrogen;  
     
     
         3 . The process according to    claim 2    wherein R 3  is a single-ringed aryl or heteroaryl group that is 5- or 6-membered, and is itself substituted at its own 4-position when a 6-membered ring or at its own 3- or 4-position when a 5-membered ring with a substituent selected from the group consisting of one other single-ringed aryl or heteroaryl group, a C 3 -C 14  alkyl group, a N-piperidyl group, a N-piperazinyl group, a phenoxy group, a thiophenoxy group, a 4-thiopyridyl group, a phenylazo group and a benzamido group.  
     
     
         4 . The process according to    claim 3    wherein R 3  contains two or more 5- or 6-membered rings.  
     
     
         5 . The process according to    claim 3    wherein R 3  when rotated about an axis drawn through the SO 2 -bonded 1-position and the substituent-bonded 4-position of a 6-membered ring or the SO 2 -bonded 1-position and substituent-bonded 3- or 4-position of a 5-membered ring, defines a three-dimensional volume whose widest dimension has the width in a direction transverse to that axis to rotation of about one furanyl ring to about two phenyl rings.  
     
     
         6 . The process according to    claim 3    wherein R 3  h as a length that is greater than that of a pentyl group and a length that is less than that of an icosyl group.  
     
     
         7 . A process for treating a host mammal having a condition associated with pathological matrix metalloprotease (MMP) activity that comprises administering a metalloprotease inhibitor compound or a pharmaceutically acceptable salt thereof in an effective amount to a mammalian host having such a condition, said metalloprotease inhibitor inhibiting the activity of one or more of MMP-2, MMP-9 and MMP-13, while exhibiting substantially less inhibitory activity against MMP-1, said compound corresponding in structure to formula II, below  
       
         
           
           
               
               
           
         
         wherein  
         R 14  is hydrido, a pharmaceutically acceptable cation or C(W)R 15  where W is O or S and R 15  is selected from the group consisting of a 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, ar-C 1 -C 6 -alkoxy, ar-C 1 -C 6 -alkyl, heteroaryl and amino C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two substituents independently selected from the group consisting of an C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkoxycarbonyl, and C 1 -C 6 -alkanoyl radical, or (iii) wherein the amino C 1 -C 6 -alkyl nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring;  
         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;  
         (a) one of X, Y and Z is selected from the group consisting of C(O), NR 6 , 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 that is selected from the group consisting of NR 6 C(O), NR S(O), NR S(O) 2 , NR 6 S, NR 6 O, SS, NR 6 NR 6  and OC(O), with the remaining one of X, Y and Z 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 hydrido, C 1 -C 6 -alkanoyl, C 6 -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, C 3 -C 8 -heterocycloalkyl, C 3 -C 8 -heterocycloalkylcarbonyl, C 6 -aryl, C 5 -C 6 -heterocyclo, C 5 -C 6 -heteroaryl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, C 6 -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, C 6 -arylsulfonyl, C 1 -C 6 -alkylsulfonyl, C 5 -C 6 -heteroarylsulfonyl, carboxy-C 1 -C 6 -alkyl, C 1 -C 4 -alkoxycarbonyl-C 1 -C 6 -alkyl, aminocarbonyl, C 1 -C 6 -alkyliminocarbonyl, C 6 -aryliminocarbonyl, C 5 -C 6 -heterocycloiminocarbonyl, C 6 -arylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, C 6 -arylthio-C 3 -C 6 -alkenyl, C 1 -C 4 -alkylthio-C 3 -C 6 -alkenyl, C 5 -C 6 -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 -C 1 -C 5 -alkylcarbonyl, hydroxy-C 1 -C 5 -alkyl, an aminocarbonyl wherein the aminocarbonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group, hydroxyaminocarbonyl, an aminosulfonyl group wherein the aminosulfonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group, an amino-C 1 -C 6 -alkylsulfonyl group wherein the amino-C 1 -C 6 -alkylsulfonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group and an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar—C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group;  
         R 7 is selected from the group consisting of a 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 a C 1 -C 6 -hydroxyalkyl group;  
         R 8  and R 9  and R 10  and R 11  are independently selected from the group consisting of a hydrido, hydroxy, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, heteroaryl, heteroar-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, heterocycloalkyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, aralkoxy-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, hydroxycarbonylar-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, the sulfoxide or sulfone of any said thio substituents, 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 an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar—C 1 -C 6 -alkyl, cycloalkyl and C 1 -C -alkanoyl, or wherein R 8  and R 9  or R 10  and R 11  and the carbon to which they are bonded form a carbonyl group, or wherein R 8  and R 9  or R 10  and Rh or R 8  and R 10  together with the atoms to which they are bonded form a 5- to 8-membered carbocyclic ring, or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms that are nitrogen, oxygen, or sulfur, with the proviso that only one of R 8  and R 9  or R 10  and R 1 l is hydroxy;  
         R 12  and R 12′  are independently selected from the group consisting of a hydrido, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, heteroaryl, heteroaralkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocycloalkyl-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, hydroxycarbonylar-C 1 -C 6 -alkyl, aminocarbonyl-C 1 -C 6 -alkyl, aryloxy-C 1 -C 6 -alkyl, heteroaryloxy-C 1 -C 6 -alkyl, CL-C 6 -alkylthio-C 1 -C 6 -alkyl, arylthio-C 1 -C 6 -alkyl, heteroarylthio-C 1 -C 6 -alkyl, the sulfoxide or sulfone of any said thio substituents, 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 an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, cycloalkyl and C 1 -C 6 -alkanoyl;  
         R 13  is selected from the group consisting of a hydrido, benzyl, phenyl, C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl and a C 1 -C 6 -hydroxyalkyl group; and  
         G-A-R-E-Y is a substituent that has a length greater than that of a pentyl group has a length that is less than that of an icosyl group wherein  
         G is an aryl or heteroaryl group;  
         A is selected from the group consisting of  
         (1) —O—;  
         (2) —S—;  
         (3) —NR 17 —;  
         (4) —CO—N(R 17 ) or —N(R 17 )—CO—, wherein R 17  is hydrogen, C 1 -C 4 -alkyl, or phenyl;  
         (5) —CO—O— or —C—CO—;  
         (6) —O—CO—O—;  
         (7) —HC═CH—;  
         (8) —NH—CO—NH—;  
         (9) —C≡C—;  
         (10) —NH—CO—C— or —O—CO—NH—;  
         (11) —N═N—;  
         (12) —NH—NH—; and  
         (13) —CS—N(R 18 )— or —N(R 18 )—CS—, wherein R 18  is hydrogen C 1 -C 4 -alkyl, or phenyl; or  
         (14) A is absent and G is bonded directly to R;  
         R is a moiety selected from the group consisting of alkyl, alkoxyalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaralkyl, heterocycloalkylalkyl, cycloalkylalkyl, cycloalkoxyalkyl, heterocycloalkoxyalkyl, aryloxyalkyl, heteroaryloxyalkyl, arylthioalkyl, heteroarylthioalkyl, cycloalkylthioalkyl, and a heterocycloalkylthioalkyl group wherein the aryl or heteroaryl or cycloalkyl or heterocycloalkyl substituent is (i) unsubstituted or (ii) substituted with one or two radicals selected from the group consisting of a halo, alkyl, perfluoroalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, amino, alkoxycarbonylalkyl, alkoxy, C 1 -C 2 -alkylene-dioxy, hydroxycarbonylalkyl, hydroxycarbonylalkylamino, nitro, hydroxy, hydroxyalkyl, alkanoylamino, and a alkoxycarbonyl group, and 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 )— or —(R 19 )CO—, wherein R 19  is a heterocycloalkyl, or a cycloalkyl group;  
 (2) —CONH— or —HNCO—; and  
 (3) —CO—;  
 (4) —SO 2 —R 19 — or —R 19 —SO 2 —;  
 (5) —SO 2 —;  
 (6) —NH—SO 2 — or —SO 2 —NH—; or  
 (7) E is absent and R is bonded directly to Y; and  
 
         Y is absent or is selected from the group consisting of a hydrido, alkyl, alkoxy, haloalkyl, aryl, aralkyl, cycloalkyl, heteroaryl, hydroxy, aryloxy, aralkoxy, heteroaryloxy, heteroaralkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, alkenyl, heterocycloalkyl, cycloalkyl, trifluoromethyl, alkoxycarbonyl, and a aminoalkyl group, wherein the aryl or heteroaryl or heterocycloalkyl group is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of an alkanoyl, halo, nitro, aralkyl, aryl, alkoxy, and an amino group wherein the amino nitrogen is (i) unsubstituted or (ii) substituted with one or two groups independently selected from hydrido, alkyl, and an aralkyl group.  
       
     
     
         8 . The process according to    claim 7    wherein said -G-A-R-E-Y substituent contains two to four carbocyclic or heterocyclic rings.  
     
     
         9 . The process according to    claim 8    wherein each of the two to four rings is 6-membered.  
     
     
         10 . The process according to    claim 7    wherein said -G-A-R-E-Y substituent has a length that is greater than a hexyl group and a length that is less than that of a stearyl group.  
     
     
         11 . The process according to    claim 7    wherein A is —O— or —S—.  
     
     
         12 . The process according to    claim 7    wherein R is an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group.  
     
     
         13 . The process according to    claim 7    wherein E is absent.  
     
     
         14 . The process according to    claim 7    wherein Y is selected from the group consisting of hydrido, an alkyl, alkoxy, perfluoroalkoxy and a perfluoroalkylthio group.  
     
     
         15 . A process for treating a host mammal having a condition associated with pathological matrix metalloprotease (MMP) activity that comprises administering a metalloprotease inhibit or compound or a pharmaceutically acceptable salt thereof in an effective amount to a mammalian host having such a condition, said metalloprotease inhibitor inhibiting the activity of one or more of MMP-2, MMP-9 and MMP-13, while exhibiting substantially less inhibitory activity against MMP-1, said compound corresponding in structure to formula III, below  
       
         
           
           
               
               
           
         
         wherein  
         R 3  is a single-ringed aryl or heteroaryl group that is 5- or 6-membered, and is itself substituted at its own 4-position when a 6-membered ring and at its own 3- or 4-position when a 5-membered ring with a substituent selected from the group consisting of a thiophenoxy, 4-chloro-phenoxy, 3-chlorophenoxy, 4-methoxyphenoxy, 3-benzodioxol-5-yloxy, 3,4-dimethylphenoxy, 4-fluorophenoxy, 4-fluorothiophenoxy, phenoxy, 4-trifluoromethoxyphenoxy, 4-trifluoromethylphenoxy, 4-(trifluoromethylthio)phenoxy, 4-(trifluoromethylthio)thiophenoxy, 4-chloro-3-fluorophenoxy, 4-isopropoxyphenoxy, 4-isopropylphenoxy, (2-methyl-1,3-benzothiazol-5-yl)oxy, 4-(1H-imidazol-1-yl)phenoxy, 4-chloro-3-methylphenoxy, 3-methyl-phenoxy, 4-ethoxyphenoxy, 3,4-difluorophenoxy, 4-chloro-3-methylphenoxy, 4-fluoro-3-chlorophenoxy, 4-(1H-1,2,4-triazol-1-yl)phenoxy, 3,5-difluorophenoxy, 3,4-dichlorophenoxy, 4-cyclopentylphenoxy, 4-bromo-3-methylphenoxy, 4-bromophenoxy, 4-methylthiophenoxy, 4-phenylphenoxy, 4-benzylphenoxy, 6-quinolinyloxy, 4-amino-3-methylphenoxy, 3-methoxyphenoxy, 5,6,7,8-tetrahydro-2-naphthalenyloxy, 3-hydroxymethylphenoxy, and a 4-benzyloxyphenoxy group;  
         R 14  is hydrido, a pharmaceutically acceptable cation or C(W)R 15  where W is O or S and R 15  is selected from the group consisting of a 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, ar-C 1 -C 6 -alkoxy, ar-C 1 -C 6 -alkyl, heteroaryl and amino C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two substituents independently selected from the group consisting of an C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl-c -C 6 -alkyl, ar-C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkoxycarbonyl, and C 1 -C 6 -alkanoyl radical, or (iii) wherein the amino C 1 -C 6 -alkyl nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring;  
         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;  
         (a) one of X, Y and Z is selected from the group consisting of C(O), NR 6 , 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 that is 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, Y and Z 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 hydrido, C 1 -C 6 -alkanoyl, C 6 -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, C 3 -C 8 -heterocycloalkyl, C 3 -C 8 -heterocycloalkylcarbonyl, C 6 -aryl, C 5 -C 6 -heterocyclo, C 5 -C 6 -heteroaryl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, C 6 -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, C 6 -arylsulfonyl, C 1 -C 6 -alkylsulfonyl, C 5 -C 6 -heteroarylsulfonyl, carboxy-C 1 -C 6 -alkyl, C 1 -C 4 -alkoxycarbonyl-C 1 -C 6 -alkyl, aminocarbonyl, C 1 -C 6 -alkyliminocarbonyl, C 6 -aryliminocarbonyl, C 5 -C 6 -heterocycloiminocarbonyl, C 6 -arylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, C 6 -arylthio-C 3 -C 6 -alkenyl, C 1 -C 4 -alkylthio-C 3 -C 6 -alkenyl, C 5 -C 6 -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 -C 1 -C 5 -alkylcarbonyl, hydroxy-C 1 -C 5 -alkyl, an aminocarbonyl wherein the aminocarbonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group, hydroxyaminocarbonyl, an aminosulfonyl group wherein the aminosulfonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group, an amino-C 1 -C 6 -alkylsulfonyl group wherein the amino-C 1 -C 6 -alkylsulfonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group and an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group;  
         R 7  is selected from the group consisting of a 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 a C 1 -C 6 -hydroxyalkyl group;  
         R 8  and R 9  and R 10  and R 11  are independently selected from the group consisting of a hydrido, hydroxy, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, heteroaryl, heteroar-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, heterocycloalkyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, aralkoxy-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, hydroxycarbonylar-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, the sulfoxide or sulfone of any said thio substituents, 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 an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar—C 1 -C 6 -alkyl, cycloalkyl and C 1 -C 6 -alkanoyl, or wherein R 8  and R 9  or R 10  and R 11  and the carbon to which they are bonded form a carbonyl group, or wherein R 8  and R 9  or R 10  and R 11 , or R 8  and R 1 o together with the atoms to which they are bonded form a 5- to 8-membered carbocyclic ring, or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms that are nitrogen, oxygen, or sulfur, with the proviso that 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 a hydrido, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, heteroaryl, heteroaralkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 —alkyl, heterocycloalkyl-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, Cl—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, hydroxycarbonylar-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, the sulfoxide or sulfone of any said thio substituents, 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 an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, cycloalkyl and C 1 -C 6 -alkanoyl; and  
         R 13  is selected from the group consisting of a hydrido, benzyl, phenyl, C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl and a C 1 -C 6 -hydroxyalkyl group.  
       
     
     
         16 . The process according to    claim 15    wherein the sum of m+n+p=1 or 2.  
     
     
         17 . The process according to    claim 15    wherein Z is O, S or NR 6 .  
     
     
         18 . The process according to    claim 15    wherein R 6  is selected from the group consisting of C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, amino-C 1 -C 6 -alkyl, aminosulfonyl, heteroaryl-C 1 -C 6 -alkyl, aryloxycarbonyl, and C 1 -C 6 -alkoxycarbonyl.  
     
     
         19 . The process according to    claim 15    wherein m=n=zero, p=1, and Y is NR 6 .  
     
     
         20 . A process for treating a host mammal having a condition associated with pathological matrix metalloprotease (MMP) activity that comprises administering a metalloprotease inhibitor compound or a pharmaceutically acceptable salt thereof in an effective amount to a mammalian host having such a condition, said metalloprotease inhibitor inhibiting the activity of one or more of MMP-2, MMP-9 and MMP-13, while exhibiting substantially less inhibitory activity against MMP-1, said compound corresponding in structure to formula IV, below  
       
         
           
           
               
               
           
         
         wherein R 3  is an optionally substituted aryl or optionally substituted heteroaryl radical, and when said aryl or heteroaryl radical is substituted, the substituent is (a) selected from the group consisting of an optionally substituted cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, aralkoxy, heteroaralkoxy, aralkoxyalkyl, aryloxyalkyl, aralkanoylalkyl, arylcarbonylalkyl, aralkylaryl, aryloxyalkylaryl, aralkoxyaryl, arylazoaryl, arylhydrazinoaryl, alkylthioaryl, arylthioalkyl, alkylthioaralkyl, aralkylthioalkyl, an aralkylthioaryl radical, the sulfoxide or sulfone of any of the thio substituents, and a fused ring structure comprising two or more 5-or 6-membered rings selected from the group consisting of aryl, heteroaryl, cycloalkyl and heterocycloalkyl, and (b) is itself optionally substituted with one or more substituents independently selected from the group consisting of a cyano, perfluoroalkyl, trifluoromethoxy, trifluoromethylthio, haloalkyl, trifluoromethylalkyl, aralkoxycarbonyl, aryloxycarbonyl, hydroxy, halo, alkyl, alkoxy, nitro, thiol, hydroxycarbonyl, aryloxy, arylthio, aralkyl, aryl, arylcarbonylamino, heteroaryloxy, heteroarylthio, heteroaralkyl, cycloalkyl, heterocyclooxy, heterocyclothio, heterocycloamino, cycloalkyloxy, cycloalkylthio, heteroaralkoxy, heteroaralkylthio, aralkoxy, aralkylthio, aralkylamino, heterocyclo, heteroaryl, arylazo, hydroxycarbonylalkoxy, alkoxycarbonylalkoxy, alkanoyl, arylcarbonyl, aralkanoyl, alkanoyloxy, aralkanoyloxy, hydroxyalkyl, hydroxyalkoxy, alkylthio, alkoxyalkylthio, alkoxycarbonyl, aryloxyalkoxyaryl, arylthioalkylthioaryl, aryloxyalkylthioaryl, arylthioalkoxyaryl, hydroxycarbonylalkoxy, hydroxycarbonylalkylthio, alkoxycarbonylalkoxy, alkoxycarbonylalkylthio, amino, 
 wherein the amino nitrogen is (i) unsubstituted, or (ii) substituted with one or two substituents that are independently selected from the group consisting of an alkyl, aryl, heteroaryl, aralkyl, cycloalkyl, aralkoxycarbonyl, alkoxycarbonyl, arylcarbonyl, aralkanoyl, heteroarylcarbonyl, heteroaralkanoyl and an alkanoyl group, or (iii) wherein the amino nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring containing zero to two additional heteroatoms that are nitrogen, oxygen or sulfur and which ring itself is (a) unsubstituted or (b) substituted with one or two groups independently selected from the group consisting of an aryl, alkyl, heteroaryl, aralkyl, heteroaralkyl, hydroxy, alkoxy, alkanoyl, cycloalkyl, heterocycloalkyl, alkoxycarbonyl, hydroxyalkyl, trifluoromethyl, benzofused heterocycloalkyl, hydroxyalkoxyalkyl, aralkoxycarbonyl, hydroxycarbonyl, aryloxycarbonyl, benzofused heterocycloalkoxy, benzofused cycloalkylcarbonyl, heterocycloalkylcarbonyl, and a cycloalkylcarbonyl group, carbonylamino  
 wherein the carbonylamino nitrogen is (i) unsubstituted, or (ii) is the reacted amine of an amino acid, or (iii) substituted with one or two radicals selected from the group consisting of an alkyl, hydroxyalkyl, hydroxyheteroaralkyl, cycloalkyl, aralkyl, trifluoromethylalkyl, heterocycloalkyl, benzofused heterocycloalkyl, benzofused heterocycloalkyl, benzofused cycloalkyl, and an N,N-dialkylsubstituted alkylamino-alkyl group, or (iv) the carboxamido nitrogen and two substituents bonded thereto together form a 5- to 8-membered heterocyclo, heteroaryl or benzofused heterocycloalkyl ring that is itself unsubstituted or substituted with one or two radicals independently selected from the group consisting of an alkyl, alkoxycarbonyl, nitro, heterocycloalkyl, hydroxy, hydroxycarbonyl, aryl, aralkyl, heteroaralkyl and an amino group, 
 wherein the amino nitrogen is (i) unsubstituted, or (ii) substituted with one or two substituents that are independently selected from the group consisting of alkyl, aryl, and heteroaryl, or (iii) wherein the amino nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring, and an aminoalkyl group  
 wherein the aminoalkyl nitrogen is (i) unsubstituted, or (ii) substituted with one or two substituents independently selected from the group consisting of an alkyl, aryl, aralkyl, cycloalkyl, aralkoxycarbonyl, alkoxycarbonyl, and an alkanoyl group, or (iii) wherein the aminoalkyl nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring; and  
 Z is selected group the group consisting of O, S, NR 6 , SO, SO 2 , and NSO 2 R 7 ,  
 wherein R 6  is selected from the group consisting of hydrido, C 1 -C 5 -alkyl, C 1 -C 5 -alkanoyl, benzyl, benzoyl, C 3 -C 5 -alkynyl, C 3 -C 5 -alkenyl, C 1 -C 3 -alkoxy-C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, heteroaryl-C 1 -C 6 -alkyl, C 1 -C 5 -hydroxyalkyl, C 1 -C 5 -carboxyalkyl, C 1 -C 5 -alkoxy C 1 -C 5 -alkylcarbonyl, and NR 8 R 9 -C 1 -C 5 -alkylcarbonyl or NR 8 R 9 -C 1 -C 5 -alkyl wherein R 8  and R 9  are independently hydrido, C 1 -C 5 -alkyl, C 1 -C 5 -alkoxycarbonyl or aryl-C 1 -C 5 -alkoxycarbonyl, or NR 8 R 9  together form a heterocyclic ring containing 5- to 8-atoms in the ring; and  
 R 7  is selected from the group consisting of a 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 a C 1 -C 6 -hydroxyalkyl group.  
 
 
       
     
     
         21 . The process according to    claim 20    wherein R 3  is a single-ringed aryl or heteroaryl group that is 5- or 6-membered, and is itself substituted at its own 4-position when a 6-membered ring or at its own 3- or 4-position when a 5-membered ring with a substituent selected from the group consisting of one other single-ringed aryl or heteroaryl group, a C 3 -C 14  alkyl group, a N-piperidyl group, a N-piperazinyl group, a phenoxy group, a thiophenoxy group, a 4-thiopyridyl group, a phenylazo group and a benzamido group.  
     
     
         22 . The process according to    claim 20    wherein R 3  has a length that is greater than that of a pentyl group and a length that is less than that of an icosyl group.  
     
     
         23 . The process according to    claim 20    wherein Z is O, S or NR 6 .  
     
     
         24 . The process according to    claim 23    wherein R 6  is selected from the group consisting of C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkoxy—C 1 -C 6 -alkyl, C 1 -C 6 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl, amino-C 1 -C 6 -alkyl, aminosulfonyl, heteroaryl-C 1 -C 6 -alkyl, aryloxycarbonyl, and C 1 -C 6 -alkoxycarbonyl.  
     
     
         25 . The process according to    claim 20    wherein said R 3  radical is the substituent G-A-R-E-Y, wherein G is an aryl or heteroaryl group; 
 A is selected from the group consisting of  
 (1) —O—;  
 (2) —S—;  
 (3) —NR 17 —;  
 (4) —CO—N(R 17 ) or —N(R 17 )—CO—, wherein R 17  is hydrogen, C 1 -C 4 -alkyl, or phenyl;  
 (5) —CO—O— or —O—CO—;  
 (6) —O—CO—O—;  
 (7) —HC═CH—;  
 (8) —NH—CO—NH—;  
 (9) —C≡C—;  
 (10) —NH—CO—O— or —O—CO—NH—;  
 (11) —N═N—;  
 (12) —NH—NH—; and  
 (13) —CS—N(R 18 )— or —N(R 18 )—CS—, wherein R 18  is hydrogen C 1 -C 4 -alkyl, or phenyl; or  
 (14) A is absent and G is bonded directly to R;  
 R is a moiety selected from the group consisting of alkyl, alkoxyalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaralkyl, heterocycloalkylalkyl, cycloalkylalkyl, cycloalkoxyalkyl, heterocycloalkoxyalkyl, aryloxyalkyl, heteroaryloxyalkyl, arylthioalkyl, heteroarylthioalkyl, cycloalkylthioalkyl, and a heterocycloalkylthioalkyl group wherein the aryl or heteroaryl or cycloalkyl or heterocycloalkyl substituent is (i) unsubstituted or (ii) substituted with one or two radicals selected from the group consisting of a halo, alkyl, perfluoroalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, amino, alkoxycarbonylalkyl, alkoxy, C 1 -C 2 -alkylene-dioxy, hydroxycarbonylalkyl, hydroxycarbonylalkylamino, nitro, hydroxy, hydroxyalkyl, alkanoylamino, and a alkoxycarbonyl group, and 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 )— or —(R 19 )CO—, wherein R 19  is a heterocycloalkyl, or a cycloalkyl group;  
 (2) —CONH— or —HNCO—; and  
 (3) —CO—;  
 (4) —SO 2 —R 19 — or —R 19 —SO 2 —;  
 (5) —SO 2 —;  
 (6) —NH—SO 2 — or —SO 2 —NH—; or  
 (7) E is absent and R is bonded directly to Y; and  
 
 Y is absent or is selected from the group consisting of a hydrido, alkyl, alkoxy, haloalkyl, aryl, aralkyl, cycloalkyl, heteroaryl, hydroxy, aryloxy, aralkoxy, heteroaryloxy, heteroaralkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, alkenyl, heterocycloalkyl, cycloalkyl, trifluoromethyl, alkoxycarbonyl, and a aminoalkyl group, wherein the aryl or heteroaryl or heterocycloalkyl group is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of an alkanoyl, halo, nitro, aralkyl, aryl, alkoxy, and an amino group wherein the amino nitrogen is (i) unsubstituted or (ii) substituted with one or two groups independently selected from hydrido, alkyl, and an aralkyl group.  
 
     
     
         26 . The process according to    claim 25    wherein said -G-A-R-E-Y substituent contains two to four carbocyclic or heterocyclic rings.  
     
     
         27 . The process according to    claim 26    wherein each of the two to four rings is 6-membered.  
     
     
         28 . The process according to    claim 25    wherein said -G-A-R-E-Y substituent has a length that is greater than a hexyl group and a length that is less than that of a stearyl group.  
     
     
         29 . The process according to    claim 25    wherein A is —O— or —S—.  
     
     
         30 . The process according to    claim 25    wherein R is an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group.  
     
     
         31 . The process according to    claim 25    wherein E is absent.  
     
     
         32 . The process according to    claim 25    wherein Y is selected from the group consisting of hydrido, an alkyl, alkoxy, perfluoroalkoxy and a perfluoroalkylthio group.  
     
     
         33 . The process according to    claim 20    wherein R 3  is a radical that is comprised of a single-ringed aryl or heteroaryl group that is 5- or 6-membered, and is itself substituted at its own 4-position when a 6-membered ring and at its own 3- or 4-position when a 5-membered ring with a substituent selected from the group consisting of a thiophenoxy, 4-chlorophenoxy, 3-chlorophenoxy, 4-methoxyphenoxy, 3-benzodioxol-5-yloxy, 3,4-dimethylphenoxy, 4-fluorophenoxy, 4-fluorothiophenoxy, phenoxy, 4-trifluoromethoxy-phenoxy, 4-trifluoromethylphenoxy, 4-(trifluoromethylthio)-phenoxy, 4-(trifluoromethylthio)-thiophenoxy, 4-chloro-3-fluorophenoxy, 4-isopropoxyphenoxy, 4-isopropylphenoxy, (2-methyl-1,3-benzothiazol-5-yl)oxy, 4-(1H-imidazol-1-yl)phenoxy, 4-chloro-3-methylphenoxy, 3-methylphenoxy, 4-ethoxyphenoxy, 3,4-difluorophenoxy, 4-chloro-3-methylphenoxy, 4-fluoro-3-chlorophenoxy, 4-(1H-1,2,4-triazol-1-yl)phenoxy, 3,5-difluorophenoxy, 3,4-dichlorophenoxy, 4-cyclopentylphenoxy, 4-bromo-3-methylphenoxy, 4-bromophenoxy, 4-methylthiophenoxy, 4-phenylphenoxy, 4-benzylphenoxy, 6-quinolinyloxy, 4-amino-3-methylphenoxy, 3-methoxyphenoxy, 5,6,7,8-tetrahydro-2-naphthalenyloxy, 3-hydroxymethylphenoxy, N-piperidyl, N-piperazinyl and a 4-benzyloxyphenoxy group.  
     
     
         34 . The process according to    claim 20    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         35 . A process for treating a host mammal having a condition associated with pathological matrix metalloprotease (MMP) activity that comprises administering a metalloprotease inhibitor compound or a pharmaceutically acceptable salt thereof in an effective amount to a mammalian host having such a condition, said metalloprotease inhibitor inhibiting the activity of one or more of MMP-2, MMP-9 and MMP-13, while exhibiting substantially less inhibitory activity against MMP-1, said compound corresponding in structure to formula V, below  
       
         
           
           
               
               
           
         
         wherein  
         Z is O, S or NR 6 ;  
         W and Q are independently oxygen (O), NR 6  or sulfur (S),  
         R 6  is selected from the group consisting of C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkyl, C 3 -C 6 -alkenyl, C 3 C 6 -alkynyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, amino-C 1 -C 6 -alkyl, aminosulfonyl, heteroaryl-C 1 -C 6 -alkyl, aryloxycarbonyl, and C 1 -C 6 -alkoxycarbonyl; and  
         q is zero or one such that when q is zero, Q is absent and the trifluoromethyl group is bonded directly to the depicted phenyl ring.  
       
     
     
         36 . The process according to    claim 35    wherein q is zero.  
     
     
         37 . The process according to    claim 35    wherein W is O.  
     
     
         38 . The process according to    claim 37    wherein q is zero.  
     
     
         39 . The process according to    claim 37    wherein q is one and Q is O.  
     
     
         40 . The process according to    claim 37    wherein q is one and, Q is S.  
     
     
         41 . The process according to    claim 35    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         42 . The process according to    claim 35    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         43 . The process according to    claim 35    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         44 . The process according to    claim 35    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         45 . The process according to    claim 35    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         46 . The process according to    claim 35    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         47 . The process according to    claim 35    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         48 . The process according to    claim 35    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         49 . The process according to    claim 35    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         50 . The process according to    claim 35    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         51 . The process according to    claim 35    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         52 . A compound corresponding in structure to formula II, below, or a pharmaceutically acceptable salt thereof:  
       
         
           
           
               
               
           
         
         wherein  
         R 14  is hydrido, a pharmaceutically acceptable cation or C(W)R 15  where W is O or S and R 15  is selected from the group consisting of an 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, ar-C 1 -C 6 -alkoxy, ar-C 1 -C 6 -alkyl, heteroaryl and amino C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two substituents independently selected from the group consisting of an C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkoxycarbonyl, and C 1 -C 6 -alkanoyl radical, or (iii) wherein the amino C 1 -C 6 -alkyl nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring;  
         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;  
         (a) one of X, Y and Z is selected from the group consisting of C(O), NR 6 , O, S, S(O), S(O) 2  and NS(O) 2 R 7   1  and the remaining two of X, Y and Z are CR 8 R 9 , and CR 1  R , or  
         (b) X and Z or Z and Y together constitute a moiety that is selected from the group consisting of NR 6 C(O), NR 6 S(O), NR 6 S(O) 2 , NR 6 S, NR 6 O, SS, NR 6 NR 6  and OC(O), with the remaining one of X, Y and Z 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 hydrido, C 1 -C 6 -alkanoyl, C 6 -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, C 3 -CB-heterocycloalkyl, C 3 -C 8 -heterocycloalkylcarbonyl, C 6 -aryl, C 5 -C 6 -heterocyclo, C 5 -C 6 -heteroaryl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, C 6 -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, C 6 -arylsulfonyl, C 1 -C 6 -alkylsulfonyl, C 5 -C 6 -heteroarylsulfonyl, carboxy-C 1 -C 6 -alkyl, C 1 -C 4 -alkoxycarbonyl-C 1 -C 6 -alkyl, aminocarbonyl, C 1 -C 6 -alkyliminocarbonyl, C 6 -aryliminocarbonyl, C 5 -C 6 -heterocycloiminocarbonyl, C 6 -arylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, C 6 -arylthio-C 3 -C 6 -alkenyl, C 1 -C 4 -alkylthio-C 3 -C 6 -alkenyl, C 5 -C 6 -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 -C 1 -C 5 -alkylcarbonyl, hydroxy-C 1 -C 5 -alkyl, an aminocarbonyl wherein the aminocarbonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group, hydroxyaminocarbonyl, an aminosulfonyl group wherein the aminosulfonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group, an amino-C 1 -C 6 -alkylsulfonyl group wherein the amino-C 1 -C 6 —alkylsulfonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar—C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group and an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar—C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group;  
         R 7  is selected from the group consisting of a 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 a C 1 -C 6 -hydroxyalkyl group;  
         R 8  and R 9  and R 10  and R 11  are independently selected from the group consisting of a hydrido, hydroxy, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, heteroaryl, heteroar-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, heterocycloalkyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, aralkoxy-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, hydroxycarbonylar-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, the sulfoxide or sulfone of any said thio substituents, 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 an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar—C 1 -C 6 -alkyl, cycloalkyl and C 1 -C 6 -alkanoyl, or wherein R 8  and R 9  or R 10  and R 11  and the carbon to which they are bonded form a carbonyl group, or wherein R 8  and R 9  or R 10  and R 11 , or R 8  and R 10  together with the atoms to which they are bonded form a 5- to 8-membered carbocyclic ring, or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms that are nitrogen, oxygen, or sulfur, with the proviso that 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 a hydrido, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, heteroaryl, heteroaralkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocycloalkyl-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, hydroxycarbonylar-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, the sulfoxide or sulfone of any said thio substituents, 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 an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, cycloalkyl and C 1 -C 6 -alkanoyl;  
         R 13  is selected from the group consisting of a hydrido, benzyl, phenyl, C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl and a C 1 -C 6 -hydroxyalkyl group; and  
         G-A-R-E-Y is a substituent that has a length greater than that of a pentyl group a length that is less than that of an icosyl group, and wherein 
 G is an aryl or heteroaryl group;  
 A is selected from the group consisting of  
 (1) —O—;  
 (2) —S—;  
 (3) —NR 17 —;  
 (4) —CO—N(R 17 ) or —N(R 17 )—CO—, wherein R 17  is hydrogen, C 1 -C 4 -alkyl, or phenyl;  
 (5) —CO—O— or —O—CO—;  
 (6) —O—CO—O—;  
 (7) —HC═CH—;  
 (8) —NH—CO—NH—;  
 (9) —C≡C—;  
 (10) —NH—CO—C— or —O—CO—NH—;  
 (11) —N═N—;  
 (12) —NH—NH—; and  
 (13) —CS—N(R 18 )— or —N(R 18 )—CS—, wherein R 18  is hydrogen C 1 -C 4 -alkyl, or phenyl; or  
 (14) A is absent and G is bonded directly to R;  
 
         R is a moiety selected from the group consisting of alkyl, alkoxyalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaralkyl, heterocycloalkylalkyl, cycloalkylalkyl, cycloalkoxyalkyl, heterocycloalkoxyalkyl, aryloxyalkyl, heteroaryloxyalkyl, arylthioalkyl, heteroarylthioalkyl, cycloalkylthioalkyl, and a heterocycloalkylthioalkyl group wherein the aryl or heteroaryl or cycloalkyl or heterocycloalkyl substituent is (i) unsubstituted or (ii) substituted with one or two radicals selected from the group consisting of a halo, alkyl, perfluoroalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, amino, alkoxycarbonylalkyl, alkoxy, C 1 -C 2 -alkylene-dioxy, hydroxycarbonylalkyl, hydroxycarbonylalkylamino, nitro, hydroxy, hydroxyalkyl, alkanoylamino, and a alkoxycarbonyl group, and 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 )— or —(R 19 )CO—, wherein R 19  is a heterocycloalkyl, or a cycloalkyl group;  
 (2) —CONH— or —HNCO—; and  
 (3) —CO—;  
 (4) —SO 2 —R 19 — or —R 19 —SO 2 —;  
 (5) —SO 2 —;  
 (6) —NH—SO 2 — or —SO 2 —NH—; or  
 (7) E is absent and R is bonded directly to Y; and  
 
         Y is absent or is selected from the group consisting of a hydrido, alkyl, alkoxy, haloalkyl, aryl, aralkyl, cycloalkyl, heteroaryl, hydroxy, aryloxy, aralkoxy, heteroaryloxy, heteroaralkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, alkenyl, heterocycloalkyl, cycloalkyl, trifluoromethyl, alkoxycarbonyl, and a aminoalkyl group, wherein the aryl or heteroaryl or heterocycloalkyl group is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of an alkanoyl, halo, nitro, aralkyl, aryl, alkoxy, and an amino group wherein the amino nitrogen is (i) unsubstituted or (ii) substituted with one or two groups independently selected from hydrido, alkyl, and an aralkyl group.  
       
     
     
         53 . The compound or salt according to    claim 52    wherein said -G-A-R-E-Y substituent contains two to four carbocyclic or heterocyclic rings.  
     
     
         54 . The compound or salt according to    claim 52    wherein each of the two to four rings is 6-membered.  
     
     
         55 . The compound or salt according to    claim 52    wherein said -G-A-R-E-Y substituent has a length that is greater than a hexyl group and a length that is less than that of a stearyl group.  
     
     
         56 . The compound or salt according to    claim 52    wherein A is —O— or —S—.  
     
     
         57 . The compound or salt according to    claim 52    wherein R is an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group.  
     
     
         58 . The compound or salt according to    claim 52    wherein E is absent.  
     
     
         59 . The compound or salt according to    claim 52    wherein Y is selected from the group consisting of hydrido, an alkyl, alkoxy, perfluoroalkoxy and a perfluoroalkylthio group.  
     
     
         60 . The compound or salt according to    claim 52    wherein R 14  is hydrido.  
     
     
         61 . The compound or salt according to    claim 52    wherein W of the C(W)R 15  is O and R 15  is a 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, or aryloxy group.  
     
     
         62 . A compound corresponding in structure to formula III, below, or a pharmaceutically acceptable salt thereof  
       
         
           
           
               
               
           
         
         wherein  
         R 3  is a single-ringed aryl or heteroaryl group that is 5- or 6-membered, and is itself substituted at its own 4-position when a 6-membered ring and at its own 3- or 4-position when a 5-membered ring with a substituent selected from the group consisting of a thiophenoxy, 4-chloro-phenoxy, 3-chlorophenoxy, 4-methoxyphenoxy, 3-benzodioxol-5-yloxy, 3,4-dimethylphenoxy, 4-fluorophenoxy, 4-fluorothiophenoxy, phenoxy, 4-trifluoromethoxyphenoxy, 4-trifluoromethylphenoxy, 4-(trifluoromethylthio)phenoxy, 4-(trifluoromethylthio)thiophenoxy, 4-chloro-3-fluorophenoxy, 4-isopropoxyphenoxy, 4-isopropylphenoxy, (2-methyl-1,3-benzothiazol-5-yl)oxy, 4-(1H-imidazol-1-yl)phenoxy, 4-chloro-3-methylphenoxy, 3-methyl-phenoxy, 4-ethoxyphenoxy, 3,4-difluorophenoxy, 4-chloro-3-methylphenoxy, 4-fluoro-3-chlorophenoxy, 4-(1H-1,2,4-triazol-1-yl)phenoxy, 3,5-difluorophenoxy, 3,4-dichlorophenoxy, 4-cyclopentylphenoxy, 4-bromo-3-methylphenoxy, 4-bromophenoxy, 4-methylthiophenoxy, 4-phenylphenoxy, 4-benzylphenoxy, 6-quinolinyloxy, 4-amino-3-methylphenoxy, 3-methoxyphenoxy, 5,6,7,8-tetrahydro-2-naphthalenyloxy, 3-hydroxymethylphenoxy, and a 4-benzyloxyphenoxy group;  
         R 14  is hydrido, a pharmaceutically acceptable cation or C(W)R 15  where W is O or S and R 15  is selected from the group consisting of a 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, ar-C 1 -C 6 -alkoxy, ar-C 1 -C 6 -alkyl, heteroaryl and amino C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two substituents independently selected from the group consisting of an C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkoxycarbonyl, and C 1 -C 6 -alkanoyl radical, or (iii) wherein the amino C 1 -C 6 -alkyl nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring;  
         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; 
 (a) one of X, Y and Z is selected from the group consisting of C(O), NR 6 , 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 1 R, or  
 (b) X and Z or Z and Y together constitute a moiety that is selected from the group consisting of NR 6 C(O), NR 6 S(O), NR 6 S(O) 2 , NR 6 S, NR 6 O, SS, NR 6 NR 6  and OC(O), with the remaining one of X, Y and Z 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 hydrido, C 1 -C 6 -alkanoyl, C 6 -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, C 3 -C 8 -heterocycloalkyl, C 3 -C 8 -heterocycloalkylcarbonyl, C 6 -aryl C 5 -C 6 -heterocyclo, C 5 -C 6 -heteroaryl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, C 6 -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, C 6 -arylsulfonyl, C 1 -C 6 -alkylsulfonyl, C 5 -C 6 -heteroarylsulfonyl, carboxy-C 1 -C 6 -alkyl, C 1 -C 4 -alkoxycarbonyl-C 1 -C 6 -alkyl, aminocarbonyl, C 1 -C 6 -alkyliminocarbonyl, C 6 -aryliminocarbonyl, C 5 -C 6 -heterocycloiminocarbonyl, C 6 -arylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, C 6 -arylthio-C 3 -C 6 -alkenyl, C 1 -C 4 -alkylthio-C 3 -C 6 -alkenyl, C 5 -C 6 -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 -C 1 -C 5 -alkylcarbonyl, hydroxy-C 1 -C 5 -alkyl, an aminocarbonyl wherein the aminocarbonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group, hydroxyaminocarbonyl, an aminosulfonyl group wherein the aminosulfonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group, an amino-C 1 -C 6 -alkylsulfonyl group wherein the amino-C 1 -C 6 .-alkylsulfonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group and an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group;  
         R 7  is selected from the group consisting of a 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 a C 1 -C 6 -hydroxyalkyl group;  
         R 8  and R 9  and R 10  and R 11  are independently selected from the group consisting of a hydrido, hydroxy, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, heteroaryl, heteroar-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, heterocycloalkyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, aralkoxy-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, hydroxycarbonylar-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, the sulfoxide or sulfone of any said thio substituents, 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 an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, cycloalkyl and C 1 -C 6 -alkanoyl, or wherein R 8  and R 9  or R 10  and R 11  and the carbon to which they are bonded form a carbonyl group, or wherein R 8  and R 9  or R 10  and R 11 , or R 8  and R 10  together with the atoms to which they are bonded form a 5- to 8-membered carbocyclic ring, or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms that are nitrogen, oxygen, or sulfur, with the proviso that 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 a hydrido, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, heteroaryl, heteroaralkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocycloalkyl-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, hydroxycarbonylar-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, the sulfoxide or sulfone of any said thio substituents, 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 an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, cycloalkyl and C 1 -C 6 -alkanoyl; and  
         R 13  is selected from the group consisting of a hydrido, benzyl, phenyl, C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl and a C 1 -C 6 -hydoy group.  
       
     
     
         63 . The compound or salt according to    claim 62    wherein the sum of m+n+p=1 or 2.  
     
     
         64 . The compound or salt according to    claim 62    wherein Z is O, S or NR 6 .  
     
     
         65 . The compound or salt according to    claim 62    wherein R 6  is selected from the group consisting of C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, amino-C 1 -C 6 -alkyl, aminosulfonyl, heteroaryl-C 1 -C 6 -alkyl, aryloxycarbonyl, and C 1 -C 6 -alkoxycarbonyl.  
     
     
         66 . The compound or salt according to    claim 62    wherein m=n=zero, p=1, and Y is NR 6 .  
     
     
         67 . The compound or salt according to    claim 62    wherein R 14  is hydrido.  
     
     
         68 . The compound or salt according to    claim 62    wherein W of the C(W)R 15  is O and R 15  is a  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, or aryloxy group.  
     
     
         69 . A compound corresponding in structure to formula IV, below, or a pharmaceutically acceptable salt thereof  
       
         
           
           
               
               
           
         
         wherein R 3  is a single-ringed aryl or heteroaryl group that is 5- or 6-membered, and is itself substituted at its own 4-position when a 6-membered ring or at its own 3- or 4-position when a 5-membered ring with a substituent selected from the group consisting of one other single-ringed aryl or heteroaryl group, a C 3 -C 14  alkyl group, a N-piperidyl group, a N-piperazinyl group, a phenoxy group, a thiophenoxy group, a 4-thiopyridyl group, a phenylazo group and a benzamido group; and  
         Z is selected group the group consisting of O, S, NR 6 , SO, SO 2 , and NSO 2 R 7 ,  
         wherein R 6  is selected from the group consisting of hydrido, C 1 -C 5 -alkyl, C 1 -C 5 -alkanoyl, benzyl, benzoyl, C 3 -C 5 -alkynyl, C 3 -C 5 -alkenyl, C 1 -C 3 -alkoxy-C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, heteroaryl-C 1 -C 6 -alkyl, C 1 -C 5 -hydroxyalkyl, C 1 -C 5 -carboxyalkyl, C 1 -C 5 -alkoxy C 1 -C 5 -alkylcarbonyl, and NR 8 R 9 -C 1 -C 5 alkylcarbonyl or NR 8 R 9 -C 1 -C 5 -alkyl wherein R 8  and R 9  are independently hydrido, C 1 -,C 5 -alkyl, C 1 -C 5 alkoxycarbonyl or aryl-C 1 -C 5 -alkoxycarbonyl, or NR 8 R 9  together form a heterocyclic ring containing 5- to 8atoms in the ring; and  
         R 7  is selected from the group consisting of a 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 a C 1 -C 6 -hydroxyalkyl group.  
       
     
     
         70 . The compound or salt according to    claim 69    wherein R 3  has a length that is greater than that of a pentyl group and a length that is less than that of an icosyl group.  
     
     
         71 . The compound or salt according to    claim 69    wherein Z is O, S or NR 6 .  
     
     
         72 . The compound or salt according to    claim 69    wherein R 6  is selected from the group consisting of C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl, amino-C 1 -C 6 -alkyl, aminosulfonyl, heteroaryl-C 1 -C 6 -alkyl, aryloxycarbonyl, and C 1 -C 6 -alkoxycarbonyl.  
     
     
         73 . The compound or salt according to    claim 69    wherein said R 3  radical is the substituent G-A-R-E-Y, wherein 
 G is an aryl or heteroaryl group;  
 A is selected from the group consisting of  
 (1) —O—;  
 (2) —S—;  
 (3) —NR 17 —;  
 (4) —CO—N(R 17 ) or —N(R 17 )—CO—, wherein R 17  is hydrogen, C 1 -C 4 -alkyl, or phenyl;  
 (5) —CO—O— or —O—CO—;  
 (6) —O—CO—O—;  
 (7) —HC═CH—;  
 (8) —NH—CO—NH—;  
 (9) —C≡C—;  
 (10) —NH—CO—O— or —O—CO—NH—;  
 (11) —N═N—;  
 (12) —NH—NH—; and  
 (13) —CS—N(R 18 )— or —N(R 18 )—CS—, wherein R 18  is hydrogen C 1 -C 4 -alkyl, or phenyl; or  
 (14) A is absent and G is bonded directly to R;  
 R is a moiety selected from the group consisting of alkyl, alkoxyalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaralkyl, heterocycloalkylalkyl, cycloalkylalkyl, cycloalkoxyalkyl, heterocycloalkoxyalkyl, aryloxyalkyl, heteroaryloxyalkyl, arylthioalkyl, heteroarylthioalkyl, cycloalkylthioalkyl, and a heterocycloalkylthioalkyl group wherein the aryl or heteroaryl or cycloalkyl or heterocycloalkyl substituent is (i) unsubstituted or (ii) substituted with one or two radicals selected from the group consisting of a halo, alkyl, perfluoroalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, amino, alkoxycarbonylalkyl, alkoxy, C 1 -C 2 -alkylene-dioxy, hydroxycarbonylalkyl, hydroxycarbonylalkylamino, nitro, hydroxy, hydroxyalkyl, alkanoylamino, and a alkoxycarbonyl group, and 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 )— or —(R 19 )CO—, wherein R 19  is a heterocycloalkyl, or a cycloalkyl group;  
 (2) —CONH— or —HNCO—; and  
 (3) —CO—;  
 (4) —SO 2 —R 19 — or —R 19 —SO 2 —;  
 (5) —SO 2 —;  
 (6) —NH—SO 2 — or —SO 2 —NH—; or  
 (7) E is absent and R is bonded directly to Y; and  
 Y is absent or is selected from the group consisting of a hydrido, alkyl, alkoxy, haloalkyl, aryl, aralkyl, cycloalkyl, heteroaryl, hydroxy, aryloxy, aralkoxy, heteroaryloxy, heteroaralkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, alkenyl, heterocycloalkyl, cycloalkyl, trifluoromethyl, alkoxycarbonyl, and a aminoalkyl group, wherein the aryl or heteroaryl or heterocycloalkyl group is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of an alkanoyl, halo, nitro, aralkyl, aryl, alkoxy, and an amino group wherein the amino nitrogen is (i) unsubstituted or (ii) substituted with one or two groups independently selected from hydrido, alkyl, and an aralkyl group.  
 
     
     
         74 . The compound or salt according to    claim 69    wherein said -G-A-R-E-Y substituent contains two to four carbocyclic or heterocyclic rings.  
     
     
         75 . The compound or salt according to    claim 69    wherein each of the two to four rings is 6-membered.  
     
     
         76 . The compound or salt according to    claim 69    wherein said -G-A-R-E-Y substituent has a length that is greater than a hexyl group and a length that is less than that of a stearyl group.  
     
     
         77 . The compound or salt according to    claim 69    wherein A is —O— or —S—.  
     
     
         78 . The compound or salt according to    claim 69    wherein R is an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group.  
     
     
         79 . The compound or salt according to    claim 69    wherein E is absent.  
     
     
         80 . The compound or salt according to    claim 69    wherein Y is selected from the group consisting of hydrido, an alkyl, alkoxy, perfluoroalkoxy and a perfluoroalkylthio group.  
     
     
         81 . The compound or salt according to    claim 69    wherein R 3  is a radical that is comprised of a single-ringed aryl or heteroaryl group that is 5-or 6-membered, and is itself substituted at its own 4-position when a 6-membered ring and at its own 3-or 4-position when a 5-membered ring with a substituent selected from the group consisting of a thiophenoxy, 4-chlorophenoxy, 3-chlorophenoxy, 4-methoxyphenoxy, 3-benzodioxol-5-yloxy, 3,4-dimethylphenoxy, 4-fluorophenoxy, 4-fluorothiophenoxy, phenoxy, 4-trifluoromethoxyphenoxy, 4-trifluoromethylphenoxy, 4-(trifluoromethylthio)phenoxy, 4-(trifluoromethylthio)thiophenoxy, 4-chloro-3-fluorophenoxy, 4-isopropoxyphenoxy, 4-isopropylphenoxy, (2-methyl-1,3-benzothiazol-5-yl)oxy, 4-(1H-imidazol-1-yl)phenoxy, 4-chloro-3-methylphenoxy, 3-methylphenoxy, 4-ethoxyphenoxy, 3,4-difluorophenoxy, 4-chloro-3-methylphenoxy, 4-fluoro-3-chlorophenoxy, 4-(1H-1,2,4-triazol-1-yl)phenoxy, 3,5-difluorophenoxy, 3,4-dichlorophenoxy, 4-cyclopentylphenoxy, 4-bromo-3-methylphenoxy, 4-bromophenoxy, 4-methylthiophenoxy, 4-phenylphenoxy, 4-benzylphenoxy, 6-quinolinyloxy, 4-amino-3-methylphenoxy, 3-methoxyphenoxy, 5,6,7,8-tetrahydro-2-naphthalenyloxy, 3-hydroxymethylphenoxy, N-piperidyl, N-piperazinyl and a 4-benzyloxyphenoxy group.  
     
     
         82 . The compound or salt according to    claim 69    wherein said R 3  group is a PhR 23  group, wherein Ph is a phenyl ring that is substituted at its 4-position by an R 23  group that is a substituent selected from the group consisting of another single-ringed aryl or heteroaryl group, a piperidyl group, a piperazinyl group, a phenoxy group, a thiophenoxy group, a phenylazo group and a benzamido group.  
     
     
         83 . The compound or salt according to    claim 82    wherein said R 23  group is itself substituted with a moiety that is selected from the group consisting of a halogen, a C 1 -C 4  alkoxy group, a C 1 -C 4  alkyl group, a dimethylamino group, a carboxyl C 1 -C 3  alkylene group, a C 1 -C 4  alkoxy carbonyl C 1 -C 3  alkylene group, a trifluoromethylthio group, a trifluoromethoxy group, a trifluoromethyl group and a carboxamido C 1 -C 3  alkylene group, or is substituted at the meta- and para-positions by a methylenedioxy group.  
     
     
         84 . The compound or salt according to    claim 83    wherein said R 23  group is substituted at the para-position.  
     
     
         85 . The compound or salt according to    claim 84    wherein said R 23  group is phenoxy.  
     
     
         86 . The compound or salt according to    claim 69    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         87 . A compound corresponding in structure to formula V, below, or a pharmaceutically acceptable salt thereof  
       
         
           
           
               
               
           
         
         wherein  
         Z is O, S or NR 6 ;  
         W and Q are independently oxygen (O), NR 6  or sulfur (S),  
         R 6  is selected from the group consisting of C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, amino-C 1 -C 6 -alkyl, aminosulfonyl, heteroaryl-C 1 -C 6 -alkyl, aryloxycarbonyl, and C 1 -C 6 -alkoxycarbonyl; and  
         q is zero or one such that when q is zero, Q is absent and the trifluoromethyl group is bonded directly to the depicted phenyl ring.  
       
     
     
         88 . The compound or salt according to    claim 87    wherein q is zero.  
     
     
         89 . The compound or salt according to    claim 87    wherein W is O.  
     
     
         90 . The compound or salt according to    claim 89    wherein q is zero.  
     
     
         91 . The compound or salt according to    claim 89    wherein q is one and Q is O.  
     
     
         92 . The compound or salt according to    claim 89    wherein q is one and Q is S.  
     
     
         93 . The compound or salt according to    claim 87    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         94 . The compound or salt according to    claim 87    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         95 . The compound or salt according to    claim 87    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         96 . The compound or salt according to    claim 87    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         97 . The compound or salt according to    claim 87    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         98 . The compound or salt according to    claim 87    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         99 . The compound or salt according to    claim 87    wherein said inhibitor corresponds in  
       
         
           
           
               
               
           
         
       
     
     
         100 . The compound or salt according to    claim 87    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         101 . The compound or salt according to    claim 100    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         102 . The compound or salt according to    claim 87    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         103 . The compound or salt according to    claim 87    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         104 . The compound or salt according to    claim 87    wherein said inhibitor corresponds in structure to the formula  
       
         
           
           
               
               
           
         
       
     
     
         105 . A compound corresponding in structure to formula VI, below  
       
         
           
           
               
               
           
         
         wherein  
         g is zero, 1 or 2;  
         R 3  is an optionally substituted aryl or optionally substituted heteroaryl radical, and when said aryl or heteroaryl radical is substituted, the substituent is (a) selected from the group consisting of an optionally substituted cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, aralkoxy, heteroaralkoxy, aralkoxyalkyl, aryloxyalkyl, aralkanoylalkyl, arylcarbonylalkyl, aralkylaryl, aryloxyalkylaryl, aralkoxyaryl, arylazoaryl, arylhydrazinoaryl, alkylthioaryl, arylthioalkyl, alkylthioaralkyl, aralkylthioalkyl, an aralkylthioaryl radical, the sulfoxide or sulfone of any of the thio substituents, and a fused ring structure comprising two or more 5-or 6-membered rings selected from the group consisting of aryl, heteroaryl, cycloalkyl and heterocycloalkyl, and (b) is itself optionally substituted with one or more substituents independently selected from the group consisting of a cyano, perfluoroalkyl, trifluoromethoxy, trifluoromethylthio, haloalkyl, trifluoromethylalkyl, aralkoxycarbonyl, aryloxycarbonyl, hydroxy, halo, alkyl, alkoxy, nitro, thiol, hydroxycarbonyl, aryloxy, arylthio, aralkyl, aryl, arylcarbonylamino, heteroaryloxy, heteroarylthio, heteroaralkyl, cycloalkyl, heterocyclooxy, heterocyclothio, heterocycloamino, cycloalkyloxy, cycloalkylthio, heteroaralkoxy, heteroaralkylithiol, aralkoxy, aralkylthio, aralkylamino, heterocyclo, heteroaryl, arylazo, hydroxycarbonylalkoxy, alkoxycarbonylalkoxy, alkanoyl, arylcarbonyl, aralkanoyl, alkanoyloxy, aralkanoyloxy, hydroxyalkyl, hydroxyalkoxy, alkylthio, alkoxyalkylthio, alkoxycarbonyl, aryloxyalkoxyaryl, arylthioalkylthioaryl, aryloxyalkylthioaryl, arylthioalkoxyaryl, hydroxycarbonylalkoxy, hydroxycarbonylalkylthio, alkoxycarbonylalkoxy, alkoxycarbonylalkylthio, amino, 
 wherein the amino nitrogen is (i) unsubstituted, or (ii) substituted with one or two substituents that are independently selected from the group consisting of an alkyl, aryl, heteroaryl, aralkyl, cycloalkyl, aralkoxycarbonyl, alkoxycarbonyl, arylcarbonyl, aralkanoyl, heteroarylcarbonyl, heteroaralkanoyl and an alkanoyl group, or (iii) wherein the amino nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring containing zero to two additional heteroatoms that are nitrogen, oxygen or sulfur and which ring itself is (a) unsubstituted or (b) substituted with one or two groups independently selected from the group consisting of an aryl, alkyl, heteroaryl, aralkyl, heteroaralkyl, hydroxy, alkoxy, alkanoyl, cycloalkyl, heterocycloalkyl, alkoxycarbonyl, hydroxyalkyl, trifluoromethyl, benzofused heterocycloalkyl, hydroxyalkoxyalkyl, aralkoxycarbonyl, hydroxycarbonyl, aryloxycarbonyl, benzofused heterocycloalkoxy, benzofused cycloalkylcarbonyl, heterocycloalkylcarbonyl, and a cycloalkylcarbonyl group, carbonylamino  
 wherein the carbonylamino nitrogen is (i) unsubstituted, or (ii) is the reacted amine of an amino acid, or (iii) substituted with one or two radicals selected from the group consisting of an alkyl, hydroxyalkyl, hydroxyheteroaralkyl, cycloalkyl, aralkyl, trifluoromethylalkyl, heterocycloalkyl, benzofused heterocycloalkyl, benzofused heterocycloalkyl, benzofused cycloalkyl, and an N,N-dialkylsubstituted alkylamino-alkyl group, or (iv) the carboxamido nitrogen and two substituents bonded thereto together form a 5- to 8-membered heterocyclo, heteroaryl or benzofused heterocycloalkyl ring that is itself unsubstituted or substituted with one or two radicals independently selected from the group consisting of an alkyl, alkoxycarbonyl, nitro, heterocycloalkyl, hydroxy, hydroxycarbonyl, aryl, aralkyl, heteroaralkyl and an amino group, 
 wherein the amino nitrogen is (i} unsubstituted, or (ii) substituted with one or two substituents that are independently selected from the group consisting of alkyl, aryl, and heteroaryl, or (iii) wherein the amino nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring, and an aminoalkyl group  
 wherein the aminoalkyl nitrogen is (i) unsubstituted, or (ii) substituted with one or two substituents independently selected from the group consisting of an alkyl, aryl, aralkyl, cycloalkyl, aralkoxycarbonyl, alkoxycarbonyl, and an alkanoyl group, or (iii) wherein the aminoalkyl nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring, or is an aryl or heteroaryl group that is substituted with a nucleophilically displaceable leaving group;  
 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;  
 (a) one of X, Y and Z is selected from the group consisting of C(O), NR 6 , 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 that is selected from the group consisting of NR 6 C(O), NR 6 S(O), NR 6 S(O) 2 , NR 6 S, NR 6 O, SS, NR 6 NR 6  and OC(O), with the remaining one of X, Y and Z 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 hydrido, C 1 -C 6 -alkanoyl, C 6 -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, C 3 -C 8 -heterocycloalkyl, C 3 -C 8 -heterocycloalkylcarbonyl, C 6 -aryl, C 5 -C 6 -heterocyclo, C 5 -C 6 -heteroaryl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, C 6 -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, C 6 -arylsulfonyl, C 1 -C 6 -alkylsulfonyl, C 5 -C 6 -heteroarylsulfonyl, carboxy-C 1 -C 6 -alkyl, C 1 -C 4 -alkoxycarbonyl-C 1 -C 6 -alkyl, aminocarbonyl, C 1 -C 6 -alkyliminocarbonyl, C 6 -aryliminocarbonyl, C 5 -C 6 -heterocycloiminocarbonyl, C 6 -arylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, C 6 -arylthio-C 3 -C 6 -alkenyl, C 1 -C 4 -alkylthio-C 3 -C 6 -alkenyl, C 5 -C 6 -heteroaryl-cl-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 -C 1 -C 5 -alkylcarbonyl, hydroxy-C 1 -C 5 -alkyl, an aminocarbonyl wherein the aminocarbonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group, hydroxyaminocarbonyl, an aminosulfonyl group wherein the aminosulfonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group, an amino-C 1 -C 6 -alkylsulfonyl group wherein the amino-C 1 -C 6 -alkylsulfonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group and an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group;  
         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 a C 1 -C 6 -hydroxyalkyl group;  
         R 8  and R 9  and R 10  and R 11  are independently selected from the group consisting of a hydrido, hydroxy, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, heteroaryl, heteroar-C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocycloalkyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, aralkoxy-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, hydroxycarbonylar-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, the sulfoxide or sulfone of any said thio substituents, 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 an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, cycloalkyl and C 1 -C 6 -alkanoyl, or wherein R 8  and R 9  or R 10  and R 11  and the carbon to which they are bonded form a carbonyl group, or wherein R 8  and R 9  or R 10  and R 11 , or R 8  and R 10  together with the atoms to which they are bonded form a 5- to 8-membered carbocyclic ring, or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms that are nitrogen, oxygen, or sulfur, with the proviso that 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 a hydrido, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, heteroaryl, heteroaralkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocycloalkyl-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, hydroxycarbonylar-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, the sulfoxide or sulfone of any said thio substituents, 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 an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, cycloalkyl and C 1 -C 6 -alkanoyl;  
         R 13  is selected from the group consisting of a hydrido, benzyl, phenyl, C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl and a C 1 -C 6 -hydroxyalkyl group; and  
         R 20  is (a) —O—R 21 , wherein R 21  is selected from the group consisting of a hydrido, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl group and a pharmaceutically acceptable cation, (b) —NH—O—R 22 , wherein R 22  is a selectively removable protecting group such as a 2-tetrahydropyranyl, benzyl, p-methoxybenzyl, carbonyl-C 1 -C 6 -alkoxy, trisubstituted silyl group, an o-nitrophenyl group, and a peptide synthesis resin, wherein the trisubstituted silyl group is substituted with C 1 -C 6 -alkyl, aryl, or ar-C 1 -C 6 -alkyl or a mixture thereof, (c) —NH—O—R 14 , where R 14  is hydrido, a pharmaceutically acceptable cation or C(W)R 25  where W is O or S and R 25  is selected from the group consisting of an 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, ar-C 1 -C 6 -alkoxy, ar-C 1 -C 6 -alkyl, heteroaryl and amino C 1 -C 6 -alkyl group wherein the amino C 1 -C 6 -alkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two substituents independently selected from the group consisting of an C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkoxycarbonyl, and C 1 -C 6 -alkanoyl radical, or (iii) wherein the amino C 1 -C 6 -alkyl nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring, or (d) —NR 26 R 27 , where R 26  and R 27  are independently selected from the group consisting of a hydrido, C 1 -C 6 -alkyl, amino C 1 C 6 -alkyl, hydroxy C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl group, or R 26  and R 27  together with the depicted nitrogen atom form a 5- to 8-membered ring containing zero or one additional heteroatom that is oxygen, nitrogen or sulfur.  
       
     
     
         106 . The compound according to    claim 105    wherein R 3  is the substituent G-A-R-E-Y wherein 
 G is an aryl or heteroaryl group;  
 A is selected from the group consisting of  
 (1) —O—;  
 (2) —S—;  
 (3) —NR—;  
 (4) —CO—N(R 17 ) or —N(R 17 )—CO—, wherein R 17  is hydrogen, C 1 -C 4 -alkyl, or phenyl;  
 (5) —CO—O— or —O—CO—;  
 (6) —O—CO—O—;  
 (7) —HC═CH—;  
 (8) —NH—CO—NH—;  
 (9) —C≡C—;  
 (10) —NH—CO—O— or —O—CO—NH—;  
 (11) —N═N—;  
 (12) —NH—NH—; and  
 (13) —CS—N(R 18 )— or —N(R 18 )—CS—, wherein R 18  is hydrogen C 1 -C 4 -alkyl, or phenyl; or  
 (14) A is absent and G is bonded directly to R;  
 R is a moiety selected from the group consisting of alkyl, alkoxyalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaralkyl, heterocycloalkylalkyl, cycloalkylalkyl, cycloalkoxyalkyl, heterocycloalkoxyalkyl, aryloxyalkyl, heteroaryloxyalkyl, arylthioalkyl, heteroarylthioalkyl, cycloalkylthioalkyl, and a heterocycloalkylthioalkyl group wherein the aryl or heteroaryl or cycloalkyl or heterocycloalkyl substituent is (i) unsubstituted or (ii) substituted with one or two radicals selected from the group consisting of a halo, alkyl, perfluoroalkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, amino, alkoxycarbonylalkyl, alkoxy, C 1 -C 2 -alkylene-dioxy, hydroxycarbonylalkyl, hydroxycarbonylalkylamino, nitro, hydroxy, hydroxyalkyl, alkanoylamino, and a alkoxycarbonyl group, and 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 )— or —(R 19 )CO—, wherein R 19  is a heterocycloalkyl, or a cycloalkyl group;  
 (2) —CONH— or —HNCO—; and  
 (3) —CO—;  
 (4) —SO 2 —R 19 — or —R 19 —SO 2 —;  
 (5) —SO 2 —;  
 (6) —NH—SO 2 — or —SO 2 —NH—; or  
 (7) E is absent and R is bonded directly to Y; and  
 Y is absent or is selected from the group consisting of a hydrido, alkyl, alkoxy, haloalkyl, aryl, aralkyl, cycloalkyl, heteroaryl, hydroxy, aryloxy, aralkoxy, heteroaryloxy, heteroaralkyl, perfluoroalkoxy, perfluoroalkylthio, trifluoromethylalkyl, alkenyl, heterocycloalkyl, cycloalkyl, trifluoromethyl, alkoxycarbonyl, and a aminoalkyl group, wherein the aryl or heteroaryl or heterocycloalkyl group is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of an alkanoyl, halo, nitro, aralkyl, aryl, alkoxy, and an amino group wherein the amino nitrogen is (i) unsubstituted or (ii) substituted with one or two groups independently selected from hydrido, alkyl, and an aralkyl group.  
 
     
     
         107 . The compound according to    claim 106    wherein said -G-A-R-E-Y substituent contains two to four carbocyclic or heterocyclic rings.  
     
     
         108 . The compound according to    claim 107    wherein each of the two to four rings is 6-membered.  
     
     
         109 . The compound according to    claim 106    wherein said -G-A-R-E-Y substituent has a length that is greater than a hexyl group and a length that is less than that of a stearyl group.  
     
     
         110 . The compound according to    claim 106    wherein A is —O— or —S—.  
     
     
         111 . The compound according to    claim 106    wherein R is an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group.  
     
     
         112 . The compound according to    claim 106    wherein E is absent.  
     
     
         113 . The compound according to    claim 106    wherein Y is selected from the group consisting of hydrido, an alkyl, alkoxy, perfluoroalkoxy and a perfluoroalkylthio group.  
     
     
         114 . The compound according to    claim 105    wherein R 14  is hydrido.  
     
     
         115 . The compound according to    claim 105    wherein W of the C(W)R 25  is O and R 25  is a 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, or aryloxy group.  
     
     
         116 . The compound according to    claim 105    wherein R 3  is a single-ringed aryl or heteroaryl group that is 5- or 6-membered, and is itself substituted at its own 4-position when a 6-membered ring and at its own 3- or 4-position when a 5-membered ring with a substituent selected from the group consisting of a thiophenoxy, 4-chloro-phenoxy, 3-chlorophenoxy, 4-methoxyphenoxy, 3-benzodioxol-5-yloxy, 3,4-dimethylphenoxy, 4-fluorophenoxy, 4-fluorothiophenoxy, phenoxy, 4-trifluoromethoxyphenoxy, 4-trifluoromethylphenoxy, 4-(trifluoromethylthio)phenoxy, 4-(trifluoromethylthio)thiophenoxy, 4-chloro-3-fluorophenoxy, 4-isopropoxyphenoxy, 4-isopropylphenoxy, (2-methyl-1,3-benzothiazol-5-yl)oxy, 4-(1H-imidazol-1-yl)phenoxy, 4-chloro-3-methylphenoxy, 3-methyl-phenoxy, 4-ethoxyphenoxy, 3,4-difluorophenoxy, 4-chloro-3-methylphenoxy, 4-fluoro-3-chlorophenoxy, 4-(1H-1,2,4-triazol-1-yl)phenoxy, 3,5-difluorophenoxy, 3,4-dichlorophenoxy, 4-cyclopentylphenoxy, 4-bromo-3-methylphenoxy, 4-bromophenoxy, 4-methylthiophenoxy, 4-phenylphenoxy, 4-benzylphenoxy, 6-quinolinyloxy, 4-amino-3-methylphenoxy, 3-methoxyphenoxy, 5,6,7,8-tetrahydro-2-naphthalenyloxy, 3-hydroxymethylphenoxy, and a 4-benzyloxyphenoxy group.  
     
     
         117 . The compound according to    claim 105    wherein said selectively removable protecting group is selected from the group consisting of a 2-tetrahydropyranyl, benzyl, p-methoxybenzyloxy-carbonyl, benzyloxycarbonyl, C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkoxy-CH 2 —, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-CH 2 — and an o-nitrophenyl group.  
     
     
         118 . The compound according to    claim 105    wherein said nucleophilically displaceable leaving group is selected from the group consisting of a halo, nitro, azido, phenylsulfoxido, aryloxy, C 1 -C 6 -alkoxy, a C 1 -C 6 -alkylsulfonate or arylsulfonate group and a trisubstituted ammonium group in which the three substituents are independently aryl, ar-C 1 -C 6 -alkyl or C 1 -C 6 -alkyl.  
     
     
         119 . The compound according to    claim 105    wherein g is zero.  
     
     
         120 . The compound according to    claim 105    wherein R 20  is —NR 26 R 27 .  
     
     
         121 . The compound according to    claim 120    wherein R 2 6 and R 27  are both hydrido.  
     
     
         122 . A compound that corresponds in structure to the formula below, or a pharmaceutically acceptable salt thereof  
       
         
           
           
               
               
           
         
       
     
     
         123 . An intermediate compound that corresponds in structure to formula VII, below  
       
         
           
           
               
               
           
         
         wherein  
         g is zero, 1 or 2;  
         D is a nucleophilically displaceable leaving group;  
         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; 
 (a) one of X, Y and Z is selected from the group consisting of C(O), NR 6 , O, S, S(O), S(O) 2  and NS(O) 2 R 7   1  and the remaining two of X, Y and Z are CR 8 R 9   1  and CR 10 R 11 , or  
 (b) X and Z or Z and Y together constitute a moiety that is selected from the group consisting of NR 6 C(O), NR 6 S(O), NR 6 S(O) 2 , NR 6 S, NR 6 O, SS, NR 6 NR 6  and OC(O), with the remaining one of X, Y and Z 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 hydrido, C 1 -C 6 -alkanoyl, C 6 -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, C 3 -C 8 -heterocycloalkyl, C 3 -C 8 -heterocycloalkylcarbonyl, C 6 -aryl, C 5 -C 6 -heterocyclo, C 5 -C 6 -heteroaryl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, C 6 -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, C 6 -arylsulfonyl, C 1 -C 6 -alkylsulfonyl, C 5 -C 6 -heteroarylsulfonyl, carboxy-C 1 -C 6 -alkyl, C 1 -C 4 -alkoxycarbonyl-C 1 -C 6 -alkyl, aminocarbonyl, C -C 6 -alkyliminocarbonyl, C 6  aryliminocarbonyl, C 5 -C 6 -heterocycloiminocarbonyl, C 6 -arylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, C 6 -arylthio-C 3 -C 6 -alkenyl, C 1 -C 4 -alkylthio-C 3 -C 6 -alkenyl, C 5 -C 6 -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 -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 -C 1 -C 5 -alkylcarbonyl, hydroxy-C 1 -C 5 -alkyl, an aminocarbonyl wherein the aminocarbonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group, hydroxyaminocarbonyl, an aminosulfonyl group wherein the aminosulfonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group, an amino-C 1 -C 6 -alkylsulfonyl group wherein the amino-C 1 -C 6 -alkylsulfonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group and an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C -alkanoyl group;  
         R 7  is selected from the group consisting of a 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 a C 1 -C 6 -hydroxyalkyl group;  
         R 8  and R 9  and R 10  and R 1 l are independently selected from the group consisting of a hydrido, hydroxy, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, heteroaryl, heteroar-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, heterocycloalkyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, aralkoxy-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, hydroxycarbonylar-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, the sulfoxide or sulfone of any said thio substituents, 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 an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, cycloalkyl and C 1 -C 6 -alkanoyl, or wherein R 8  and R 9  or R 10  and R 11  and the carbon to which they are bonded form a carbonyl group, or wherein R 8  and R 9  or R 10  and R 11 , or R 8  and R 10  together with the atoms to which they are bonded form a 5- to 8-membered carbocyclic ring, or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms that are nitrogen, oxygen, or 1S sulfur, with the proviso that 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 a hydrido, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, heteroaryl, heteroaralkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocycloalkyl-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, Cl—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, hydroxycarbonylar-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, the sulfoxide or sulfone of any said thio substituents, 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 an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, cycloalkyl and C 1 -C 6 -alkanoyl;  
         R 13  is selected from the group consisting of a hydrido, benzyl, phenyl, C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl and a C 1 -C 6 -hydroxyalkyl group; and  
         R 20  is (a) —O—R 21 , wherein R 21  is selected from the group consisting of a hydrido, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl group and a pharmaceutically acceptable cation, (b) —NH—O—R 22 , wherein R 22  is a selectively removable protecting group such as a 2-tetrahydropyranyl, benzyl, p-methoxybenzyl, carbonyl-C 1 -C 6 -alkoxy, trisubstituted silyl group, an o-nitrophenyl group, and a peptide synthesis resin, wherein the trisubstituted silyl group is substituted with C 1 -C 6 -alkyl, aryl, or ar-C 1 -C 6 -alkyl or a mixture thereof, (c) —NH—O—R 14 , where R 14  is hydrido, a pharmaceutically acceptable cation or C(W)R 25  where W is O or S and R 25  is selected from the group consisting of an 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, ar-C 1 -C 6 -alkoxy, ar-C 1 -C 6 -alkyl, heteroaryl and amino C 1 -C 6 -alkyl group wherein the amino C 1 -C 6 -alkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two substituents independently selected from the group consisting of an C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkoxycarbonyl, and C 1 -C 6 -alkanoyl radical, or (iii) wherein the amino C 1 -C 6 -alkyl nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring, or (d) —NR 26 R 27 , where R 26  and R 27  are independently selected from the group consisting of a hydrido, C 1 -C 6 -alkyl, amino C 1 -C 6 -alkyl, hydroxy C 1 -C 6 -alkyl, aryl ar-C 1 -C 6 -alkyl group, or R 26  and R 27  together with the depicted nitrogen atom form a 5- to 8-membered ring containing zero or one additional heteroatom that is oxygen, nitrogen or sulfur.  
       
     
     
         124 . The compound according to    claim 123    wherein said selectively removable protecting group is selected from the group consisting of a 2-tetrahydropyranyl, C 1 -C 6 -acyl, aroyl, benzyl, p-methoxybenzyloxycarbonyl, benzyloxycarbonyl, C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkoxy-CH 2 —, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-CH 2 — and an o-nitrophenyl group.  
     
     
         125 . The compound according to    claim 123    wherein said nucleophilically displaceable leaving group, D, is selected from the group consisting of a halo, nitro, azido, phenylsulfoxido, aryloxy, C 1 -C 6 -alkoxy, a C 1 -C 6 -alkylsulfonate or arylsulfonate group and a trisubstituted ammonium group in which the three substituents are independently aryl, ar-C 1 -C 6 -alkyl or C 1 -C 6 -alkyl.  
     
     
         126 . The compound according to    claim 123    wherein said halo group is fluoro.  
     
     
         127 . The compound according to    claim 123    wherein g is zero.  
     
     
         128 . A pharmaceutical composition that comprises a compound according to    claim 52    dissolved or dispersed in a pharmaceutically acceptable carrier.  
     
     
         129 . A pharmaceutical composition that comprises a compound according to    claim 62    dissolved or dispersed in a pharmaceutically acceptable carrier.  
     
     
         130 . A pharmaceutical composition that comprises a compound according to    claim 69    dissolved or dispersed in a pharmaceutically acceptable carrier.  
     
     
         131 . A pharmaceutical composition that comprises a compound according to    claim 87    dissolved or dispersed in a pharmaceutically acceptable carrier.  
     
     
         132 . A process for forming a metalloprotease inhibitor compound product or intermediate compound product therefore that comprises the step of coupling an intermediate compound with another moiety, wherein said intermediate compound corresponds in structure to formula VIB, below, and said product corresponds in structure to formula VIA, below:  
       
         
           
           
               
               
           
         
         wherein  
         g is zero, 1 or 2;  
         R 3′  is an aryl or heteroaryl group that is substituted with a coupling substituent reactive for coupling with another moiety  
         R 3  is an optionally substituted aryl or optionally substituted heteroaryl radical, and when said aryl or heteroaryl radical is substituted, the substituent is (a) selected from the group consisting of an optionally substituted cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, aralkoxy, heteroaralkoxy, aralkoxyalkyl, aryloxyalkyl, aralkanoylalkyl, arylcarbonylalkyl, aralkylaryl, aryloxyalkylaryl, aralkoxyaryl, arylazoaryl, arylhydrazinoaryl, alkylthioaryl, arylthioalkyl, alkylthioaralkyl, aralkylthioalkyl, an aralkylthioaryl radical, the sulfoxide or sulfone of any of the thio substituents, and a fused ring structure comprising two or more 5-or 6-membered rings selected from the group consisting of aryl, heteroaryl, cycloalkyl and heterocycloalkyl, and (b) is itself optionally substituted with one or more substituents independently selected from the group consisting of a cyano, perfluoroalkyl, trifluoromethoxy, trifluoromethylthio, haloalkyl, trifluoromethylalkyl, aralkoxycarbonyl, aryloxycarbonyl, hydroxy, halo, alkyl, alkoxy, nitro, thiol, hydroxycarbonyl, aryloxy, arylthio, aralkyl, aryl, arylcarbonylamino, heteroaryloxy, heteroarylthio, heteroaralkyl, cycloalkyl, heterocyclooxy, heterocyclothio, heterocycloamino, cycloalkyloxy, cycloalkylthio, heteroaralkoxy, heteroaralkylthio, aralkoxy, aralkylthio, aralkylamino, heterocyclo, heteroaryl, arylazo, hydroxycarbonylalkoxy, alkoxycarbonylalkoxy, alkanoyl, arylcarbonyl, aralkanoyl, alkanoyloxy, aralkanoyloxy, hydroxyalkyl, hydroxyalkoxy, alkylthio, alkoxyalkylthio, alkoxycarbonyl, aryloxyalkoxyaryl, arylthioalkylthioaryl, aryloxyalkylthioaryl, arylthioalkoxyaryl, hydroxycarbonylalkoxy, hydroxycarbonylalkylthio, alkoxycarbonylalkoxy, alkoxycarbonylalkylthio, amino, 
 wherein the amino nitrogen is (i) unsubstituted, or (ii) substituted with one or two substituents that are independently selected from the group consisting of an alkyl, aryl, heteroaryl, aralkyl, cycloalkyl, aralkoxycarbonyl, alkoxycarbonyl, arylcarbonyl, aralkanoyl, heteroarylcarbonyl, heteroaralkanoyl and an alkanoyl group, or (iii) wherein the amino nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring containing zero to two additional heteroatoms that are nitrogen, oxygen or sulfur and which ring itself is (a) unsubstituted or (b) substituted with one or two groups independently selected from the group consisting of an aryl, alkyl, heteroaryl, aralkyl, heteroaralkyl, hydroxy, alkoxy, alkanoyl, cycloalkyl, heterocycloalkyl, alkoxycarbonyl, hydroxyalkyl, trifluoromethyl, benzofused heterocycloalkyl, hydroxyalkoxyalkyl, aralkoxycarbonyl, hydroxycarbonyl, aryloxycarbonyl, benzofused heterocycloalkoxy, benzofused cycloalkylcarbonyl, heterocycloalkylcarbonyl, and a cycloalkylcarbonyl group, carbonylamino  
 wherein the carbonylamino nitrogen is (i) unsubstituted, or (ii) is the reacted amine of an amino acid, or (iii) substituted with one or two radicals selected from the group consisting of an alkyl, hydroxyalkyl, hydroxyheteroaralkyl, cycloalkyl, aralkyl, trifluoromethylalkyl, heterocycloalkyl, benzofused heterocycloalkyl, benzofused heterocycloalkyl, benzofused cycloalkyl, and an N,N-dialkylsubstituted alkylamino-alkyl group, or (iv) the carboxamido nitrogen and two substituents bonded thereto together form a 5- to 8-membered heterocyclo, heteroaryl or benzofused heterocycloalkyl ring that is itself unsubstituted or substituted with one or two radicals independently selected from the group consisting of an alkyl, alkoxycarbonyl, nitro, heterocycloalkyl, hydroxy, hydroxycarbonyl, aryl, aralkyl, heteroaralkyl and an amino group, 
 wherein the amino nitrogen is (i) unsubstituted, or (ii) substituted with one or two substituents that are independently selected from the group consisting of alkyl, aryl, and heteroaryl, or (iii) wherein the amino nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring, and an aminoalkyl group  
 wherein the aminoalkyl nitrogen is (i) unsubstituted, or (ii) substituted with one or two substituents independently selected from the group consisting of an alkyl, aryl, aralkyl, cycloalkyl, aralkoxycarbonyl, alkoxycarbonyl, and an alkanoyl group, or (iii) wherein the aminoalkyl nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring;  
 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; 
 (a) one of X, Y and Z is selected from the group consisting of C(O), NR 6 , 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 1  R 11 , or  
 (b) X and Z or Z and Y together constitute a moiety that is selected from the group consisting of NR 6 C(O), NR 6 S(O), NR 6 S(O) 2 , NR 6 S, NR 6 O, SS, NR 6 NR 6  and OC(O), with the remaining one of X, Y and Z 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 hydrido, C 1 -C 6 -alkanoyl, C 6 -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, C 3 -C 8 -heterocycloalkyl, C 3 -C 8 -heterocycloalkylcarbonyl, C 6 -aryl, C 5 -C 6 -heterocyclo, C 5 -C 6 -heteroaryl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, C 6 -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, C 6 -arylsulfonyl, C 1 -C 6 -alkylsulfonyl, C 5 -C 6 -heteroarylsulfonyl, carboxy-C 1 -C 6 -alkyl, C 1 -C 4 -alkoxycarbonyl-C 1 -C 6 -alkyl, aminocarbonyl, C 1 -C 6 -alkyliminocarbonyl, C 6 -aryliminocarbonyl, C 5 -C 6 -heterocycloiminocarbonyl, C 6 -arylthio-C 1 -C 6 -alkyl, C 1 -C 6 -alkylthio-C 1 -C 6 -alkyl, C 6 -arylthio-C 3 -C 6 -alkenyl, C 1 -C 4 -alkylthio-C 3 -C 6 -alkenyl, C 5 -C 6 -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 -C 1 -C 5 -alkylcarbonyl, hydroxy-C 1 -C 5 -alkyl, an aminocarbonyl wherein the aminocarbonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group, hydroxyaminocarbonyl, an aminosulfonyl group wherein the aminosulfonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group, an amino-C 1 -C 6 -alkylsulfonyl group wherein the amino-C 1 -C 6 -alkylsulfonyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group and an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar.-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and a C 1 -C 6 -alkanoyl group;  
         R 7  is selected from the group consisting of a 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 a C 1 -C 6 -hydroxyalkyl group;  
         R 8  and R 9  and R 10  and R 11  are independently selected from the group consisting of a hydrido, hydroxy, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, heteroaryl, heteroar-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, heterocycloalkyl-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, aralkoxy-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, hydroxycarbonylar-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, the sulfoxide or sulfone of any said thio substituents, 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 an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar—C 1 -C 6 -alkyl, cycloalkyl and C 1 -C 6 -alkanoyl, or wherein R 8  and R 9  or R 10  and R 11  and the carbon to which they are bonded form a carbonyl group, or wherein R 8  and R 9  or R 10  and R 11 , or R 8  and R 10  together with the atoms to which they are bonded form a 5- to 8-membered carbocyclic ring, or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms that are nitrogen, oxygen, or sulfur, with the proviso that 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 a hydrido, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, heteroaryl, heteroaralkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl, thiol-C 1 -C 6 -alkyl, cycloalkyl, cycloalkyl-C 1 -C 6 -alkyl, heterocycloalkyl-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, hydroxycarbonylar-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, the sulfoxide or sulfone of any said thio substituents, 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 an amino-C 1 -C 6 -alkyl group wherein the aminoalkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two radicals independently selected from the group consisting of C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkyl, cycloalkyl and C 1 -C 6 -alkanoyl;  
         R 13  is selected from the group consisting of a hydrido, benzyl, phenyl, C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, C 2 -C 6 -alkenyl and a C 1 -C 6 -hydroxyalkyl group; and  
         R 20  is (a) —O—R 21 , wherein R 21  is selected from the group consisting of a hydrido, C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl group and a pharmaceutically acceptable cation, (b) —NH—O—R 22 , wherein R 22  is a selectively removable protecting group such as a 2-tetrahydropyranyl, benzyl, p-methoxybenzyl, carbonyl-C 1 -C 6 -alkoxy, trisubstituted silyl group, an o-nitrophenyl group, and a peptide synthesis resin, wherein the trisubstituted silyl group is substituted with C 1 -C 6 -alkyl, aryl, or ar-C 1 -C 6 -alkyl or a mixture thereof, (c) —NH—O—R 14 , where R 14  is hydrido, a pharmaceutically acceptable cation or C(W)R 25  where W is O or S and R 25  is selected from the group consisting of an 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, ar-C 1 -C 6 -alkoxy, ar-CL-C 6 -alkyl, heteroaryl and amino C 1 -C 6 -alkyl group wherein the amino C 1 -C 6 -alkyl nitrogen is (i) unsubstituted or (ii) substituted with one or two substituents independently selected from the group consisting of an C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, ar-C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkoxycarbonyl, and C 1 -C 6 -alkanoyl radical, or (iii) wherein the amino C 1 -C 6 -alkyl nitrogen and two substituents attached thereto form a 5- to 8-membered heterocyclo or heteroaryl ring, or (d) —NR 26 R 27 , where R 26  and R 27  are independently selected from the group consisting of a hydrido, C 1 -C 6 -alkyl, amino C 1 -C 6 -alkyl, hydroxy C 1 -C 6 -alkyl, aryl, ar-C 1 -C 6 -alkyl group, or R 26  and R 27  together with the depicted nitrogen atom form a 5- to 8-membered ring containing zero or one additional heteroatom that is oxygen, nitrogen or sulfur.  
       
     
     
         133 . The process according to    claim 132    including the further step of recovering said product.  
     
     
         134 . The process according to    claim 132    wherein R 20  is —NH—O—R 22 , wherein R 22  is a selectively removable protecting group.  
     
     
         135 . The process according to    claim 134    wherein said selectively removable protecting group is selected from the group consisting of a 2-tetrahydropyranyl, benzyl, p-methoxybenzyloxycarbonyl, benzyloxycarbonyl, C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkoxy-CH 2 —, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-CH 2 —, an o-nitrophenyl group and a peptide synthesis resin.  
     
     
         136 . The process according to    claim 132    wherein said coupling substituent is a nucleophilically displaceable leaving group  
     
     
         137 . The process according to    claim 132    wherein said nucleophilically displaceable leaving group is selected from the group consisting of a halo, nitro, azido, phenylsulfoxido, aryloxy, C 1 -C 6 -alkoxy, a C 1 -C 6 -alkylsulfonate or arylsulfonate group and a trisubstituted ammonium group in which the three substituents are independently aryl, ar-C 1 -C 6 -alkyl or C 1 -C 6 -alkyl.  
     
     
         138 . The process according to    claim 132    wherein g is 2.  
     
     
         139 . The process according to    claim 132    wherein said R 3  is an aryl or heteroaryl group.  
     
     
         140 . The process according to    claim 132    wherein said intermediate that corresponds in structure to formula VI corresponds in structure to formula VIIA, below,  
       
         
           
           
               
               
           
         
         wherein D is said nucleophilically displaceable leaving group and is selected from the group consisting of a halo, nitro, azido, phenylsulfoxido, aryloxy, C 1 -C 6 -alkoxy, a C 1 -C 6 -alkylsulfonate or arylsulfonate group and a trisubstituted ammonium group in which the three substituents are independently aryl, ar-C 1 -C 6 -alkyl or C 1 -C 6 -alkyl.  
       
     
     
         141 . The process according to    claim 132    including the further step of recovering said product.  
     
     
         142 . The process according to    claim 132    including the further step of selectively removing said protecting group, R 22 .  
     
     
         143 . The process according to    claim 142    wherein said protecting group, R 22 , is removed after carrying out the further step of recovering said product.  
     
     
         144 . The process according to    claim 143    wherein said protecting group, R 22 , is a 2-tetrahydropyranyl group.  
     
     
         145 . The process according to    claim 133    wherein R 21  in said product after recovery is hydrido, and including the further step of reacting said product with hydroxyl amine or a hydroxyl amine whose oxygen is reacted with a selectively removable protecting group selected from the group consisting of a 2-tetrahydropyranyl, C 1 -C 6 -acyl, aroyl, benzyl, p-methoxybenzyloxycarbonyl, benzyloxycarbonyl, C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkoxy-CH 2 —, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-CH 2 —, an o-nitrophenyl group and a peptide synthesis resin to form a hydroxamic acid or protected hydroxamate product.  
     
     
         146 . The process according to    claim 145    including the further step of recovering the product formed.