Patent ID: 6451791
Filing Date: 2002-09-17
Classification: A61P,C07C,C07D

Abstract:
A compound or a salt thereof, wherein:the compound or salt is characterizeable in that the compound or salt selectively inhibits in vitro activity of human MMP)-2, human MMP-3, and/or human MMP-13 over in vitro activity of human MMP-1; the compound corresponds in structure to Formula VII: n is selected from the group consisting of zero, 1, and 2; W isâ€”NR5COR6; R1 is selected from the group consisting of cycloalkylene, arylene, and heteroarylene; R2 is selected from the group consisting of alkyl, aralkyl, heteroaralkyl, cycloalkylalkyl, heterocycloalkylalkyl, hydroxycarbonylalkyl, aroylalkyl, and heteroaroylalkyl; R3 is selected from the group consisting of hydrido, alkyl, aryl, aralkyl, thioalkyl, heteroaralkyl, heteroaryl, alkoxyalkoxyalkyl, trifluoromethylalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, hydroxycarbonylalkyl, alkoxyalkyl, heterocycloalkylalkyl, aryloxyalkyl, alkylthioalkyl, arylthioalkyl, heteroarylthioalkyl, a sulfoxide of any said thio-containing substituents, a sulfone of any said thio-containing substituents, â€”(CH2)xâ€”C(O)NR11R12, and â€”(CH2)yâ€”W1; each x is an integer from zero to 6; y is an integer from I to 6; R4 is selected from the group consisting of hydrido and C1-C4 alkyl; as to R5 and R6: R5 is selected from the group consisting of hydrido and C1-C4 alkyl; and R6 is selected from the group consisting of hydrido, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, alkylthioalkyl, and â€”(CH2)xâ€”NR11R12, wherein: any aryl or heteroaryl of R6 is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-C6 alkyl, C1-C4 alkoxy, nitro, cyano, hydroxy, carboxy, hydroxycarbonylalkyl, â€”(CH2)xâ€”NR11R12, trifluoromethyl, alkoxycarbonyl, aminocarbonyl, thio, alkylsulfonyl, carbonylamino, aminosulfonyl, alkylsulfonamino, alkoxyalkyl, cycloalkyloxy, alkylthioalkyl, and alkylthio, or R5 and R6, together with the atoms to which they are bonded, form an optionally substituted 5- or 7-membered cyclic amide or imide; as to each pair of R11 and R12: R11 and R12 are independently selected from the group consisting of hydrido, alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, cycloalkyl, alkanoyl, aralkanoyl, and heteroaralkanoyl, or R11 and R12, together with the atom to which they are bonded, form a 5- to 8-membered heterocyclo or heteroaryl ring; R13 is selected from the group consisting of hydrido and C1-C6 alkyl; R14 is selected from the group consisting of hydrido, C1-C6 alkyl, optionally substituted aryl, optionally substituted arylalkyl, and tetrahydropyranyl; W1 is selected from the group consisting of â€”NR5aCOR6a, NR5aS(O)zR7, â€”NR5aCOOR8, â€”NR5aCONR8R9, and NR11R12; z is selected from the group consisting of zero, 1, and 2; as to R5a, R6a, R7, R8, and R9: R5a is selected from the group consisting of hydrido and C1-C4 alkyl, and R6a is selected from the group consisting of hydrido, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, alkylthioalkyl, and â€”(CH2)xâ€”NR11R12, R5a and R6a, together with the atoms to which they are bonded, form an optionally substituted 5- or 7-membered cyclic amide or imide, R5a is selected from the group consisting of hydrido and C1-C4 alkyl, and R7 is selected from the group consisting of hydrido, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, alkylthioalkyl, and â€”(CH2)xâ€”NR11R12, R5a and R7, together with the atoms to which they are bonded, form an optionally substituted 5- or 7-membered cyclic sulfonamide, R5a is selected from the group consisting of hydrido and C1-C4 alkyl, and R8 and R9 are independently selected from the group consisting of hydrido, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, alkylthioalkyl, and â€”(CH2)xâ€”NR11R12, or R5a is selected from the group consisting of hydrido and C1-C4 alkyl, and R8 and R9, together with the atom to which they are bonded, form a 5- to 7-membered ring having no greater than one ring atom selected from the group consisting of oxygen, nitrogen, and sulfur, with the remaining ring atoms being carbon; and any aryl or heteroaryl of R6a, R7, R8, or R9 is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-C4 alkyl, C1-C4 alkoxy, nitro, cyano, hydroxy, carboxy, hydroxycarbonylalkyl, â€”(CH2)xâ€”NR11R12, trifluoromethyl, alkoxycarbonyl, aminocarbonyl, thio, alkylsulfonyl, carbonylamino, aminosulfonyl, alkylsulfonamino, alkoxyalkyl, cycloalkyloxy, alkylthioalkyl, and alkylthio.