Macrocyclic compounds as metalloprotease inhibitors

A compound of formula I:

• or pharmaceutically acceptable salts or prodrug forms thereof, wherein;
• R2 is selected from H, —CO2R5, —CONR6R5, —CONR6(OR5), -alkyl, -alkylaryl, -alkylheteroaryl, -alkylheterocyclic, -aryl, heteroaryl or -heterocyclic which is substituted with one or more substituents selected from:
• hydrogen, halo, hydroxy, alkoxy, aryloxy, phenoxy, amino, mono-alkylamino, di-alkylamino, acylamino, acetamido, benzamido, arylamino, guanidino, N-methyl imidazolyl, imidazolyl, indolyl, mercapto, lower alkylthio, arylthio, phenylthio, carboxy, sulfonamido, carboxamido, or carboalkoxy;
• R5 is selected from:
• —(CHR1Y)n—R9, —C(R7R8)n—W—C(R7R8)m—R9,
• —C(R7R8)m—R9, —C(R7R8)m-aryl,
• —C(R7R8)mCONR7R8,
• —C(R7R8)m-heteroaryl,
• —C(R7R8)m-heterocyclic;
• R6 is selected from:
• H, alkyl-, —(C1-C6)alkyl-aryl, —(C1-C6)alkyl-heteroaryl, —(C1-C6)alkyl-heterocyclic, —(C1-C6)alkyl-acyl;
• Alternatively, R5 and R6 may form a 3 to 8 membered ring optionally unsaturated containing from 1 to 3 heteroatoms selected from —O, —NR6, —S(O)p, or an acyl group, optionally fused to an aryl ring;
• R7 and R8 may be selected independently from:
• H, R11, or form a 3 to 7 membered substituted ring with 0-3 unsaturations,
• wherein the substituent is selected from;
• hydrogen, C1-C5 alkyl, hydroxy, halo, alkoxy, amino, mono-alkylamino, di-alkylamino, acylamino, thio, thioalkyl, carboxy, carboamido or aryl, optionally containing —O—, —S(O)p, —NR6, optionally fused to a substituted aryl ring,
• wherein the substituent is selected from;
• hydrogen, C1-C5 alkyl, hydroxy, halo, alkoxy, amino, mono-alkylamino, di-alkylamino, acylamino, thio, thioalkyl, carboxy, carboxamido or aryl;
• R9 is H, alkyl, cycloalkyl, 5 or 6 membered ring optionally containing from 1 to 2 N, O or S(O)p, optionally substituted with —OH, —O—(C1-C6)alkyl, —O-acyl-alkyl, NHR10, or aryl;
• R10 is H or an optionally substituted alkyl group;
• R11 is selected from:
• H,
• —(C0-C6)alkyl-S(O)p-(C1-C6)alkyl,
• —(C0-C6)alkyl-O—(C1-C6)alkyl,
• —(C0-C6)alkyl-S(O)p-(C0-C6)alkyl-aryl,
• —(C0-C6)alkyl-O—(C0-C6)alkyl-aryl,
• alkyl of from 1 to 20 carbon atoms which may be branched, cyclic and unsaturated alkyl groups, substituted alkyl
• wherein the substituent is selected from;
• hydrogen, halo, hydroxy, alkoxy, aryloxy, phenoxy, amino, mono-alkylamino, di-alkylamino, acylamino, acetamido, benzamido, arylamino, guanidino, N-methyl imidazolyl, imidazolyl, indolyl, mercapto, alkylthio, arylthio, phenylthio, carboxy, carboxamido, carbo alkoxy, or sulfonamido,
• —(C0-C8)alkyl-aryl,
• —(C0-C8)alkyl-substituted aryl,
• —(C0-C8)aryl-(C1-C4)alkyl-aryl,
• —(C1-C8)alkyl-biaryl,
• —(C0-C8)alkyl-S(O)p-(C0-C8)alkyl-aryl,
• —(C0-C8)alkyl-S(O)p-(C0-C8)alkyl-substituted aryl,
• —(C1-C4)alkyl-aryl-(C0-C8)alkyl-aryl-[S(O)p-(C0-C8)alkyl],
• —(C0-C8)alkyl-S(O)p-(C0-C8)alkyl-biaryl,
• —(C0-C8)alkyl-O—(C0-C8)alkyl-aryl,
• —(C0-C8)alkyl-S(O)p-(C0-C8)alkyl-substituted aryl,
• —(C1-C4)alkyl-aryl-(C0-C8)alkyl-aryl-[O—(C0-C8)alkyl],
• —(C0-C8)alkyl-O—(C0-C8)alkyl-biaryl,
• —(C0-C8)alkyl-O—(C0-C8)alkyl-substituted aryl,
• wherein the substituent is selected from;
• hydrogen, C1-C5 alkyl, hydroxy, halo, alkoxy, amino, mono-alkylamino, di-alkylamino, acylamino, thio, thioalkyl, carboxy, carboamido or aryl;
• m is an integer from 0 to 5;
• n is an integer from 1 to 5;
• p can be 0, 1 or 2;
• W is —O—, S(O)p or NR10;
• Y is selected from:
• —CONR10—, —NR10CO—, —SO2NR10—, —NR10SO2—, a 5 membered heterocyclic ring saturated, unsaturated or partially unsaturated containing from 1 to 4 heteroatoms selected from N, O or S.