Lactam metalloprotease inhibitors

A compound of formula I:

• or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein;
• A is selected from COR5, —CO2H, CH2CO2H, —CO2R6, —CONHOH, —CONHOR5, —CONHOR6, —NHRa, —N(OH)COR5, —SH, —CH2SH, —SO2NHRa, SN2H2Ra, PO(OH)2, and PO(OH)NHRa;
• ring B is a 5 membered cyclic amide containing 0-1 additional carbonyl groups and 0-1 double bonds;
• R1 is U—X—Y—Z—Ua—Xa—Ya—Za;
• U is absent or is selected from:
• O, NRa, C(O), C(O)O, OC(O), C(O)NRa, NRaC(O), OC(O)O, OC(O)NRa, NRaC(O)O, NRaC(O)NRa, S(O)p, S(O)pNRa, NRaS(O)p, and NRaSO2NRa;
• X is absent or selected from C1-10 alkylene, C2-10 alkenylene, and C2-10 alkynylene;
• Y is absent or selected from O, NRa, S(O)p, and C(O);
• Z is selected from a C3-13 carbocyclic residue substituted with 0-5 Rb and a 5-14 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-5 Rb;
• Ua is absent or is selected from:
• O, NRa, C(O), C(O)O, OC(O), C(O)NRa, NRaC(O), OC(O)O, OC(O)NRa, NRaC(O)O, NRaC(O)NRa, S(O)p, S(O)pNRa, NRaS(O)p, and NRaSO2NRa;
• Xa is absent or selected from C1-10 alkylene, C2-10 alkenylene, C2-10 alkynylene;
• Ya is absent or selected from O, NRa, S(O)p, and C(O);
• Za is selected from H, a C3-13 carbocyclic residue substituted with 0-5 Rc and a 5-14 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-5 Rc;
• provided that one of Z and Za is a heterocycle and Za is other than quinolinyl;
• R2 is selected from H, Q′, C1-10 alkylene-Q′, C2-10 alkenylene-Q′, C2-10 alkynylene-Q′, (CRR′)r′O(CRR′)r—Q′, (CRR′)r′NRa(CRR′)r—Q′, (CRR′)r′NRaC(O)(CRR′)r—Q′, (CRR′)r′C(O)NRa(CRR′)r—Q′, (CRR′)r′C(O)(CRR′)r—Q′, (CRR′)r′C(O)O(CRR′)r—Q′, (CRR′)r′S(O)p(CRR′)r—Q′, (CRR′)r′SO2NRa(CRR′)r—Q′, (CRR′)r′NRaC(O)NRa(CRR′)r—Q′, (CRR′)r′OC(O)NRa(CRR′)r—Q′, and (CRR′)r′NRaC(O)O(CRR′)r—Q′;
• R, at each occurrence, is independently selected from H, CH3, CH2CH3, CH═CH2, CH═CHCH3, and CH2CH═CH2;
• R′, at each occurrence, is independently selected from H, CH3, CH2CH3, and CH(CH3)2;
• Q′ is selected from H and a C3-13 carbocyclic residue substituted with 0-5 Rb;
• R3 is selected from H, Q, C1-10 alkylene-Q, C2-10 alkenylene-Q, C2-10 alkynylene-Q, (CRR′)r′O(CRR′)r—Q, (CRR′)r′NRa(CRR′)r—Q, (CRR′)rC(O)(CRR′)r—Q, (CRR′)rC(O)O(CRR′)rQ, (CRR′)r′OC(O) (CRR′)r—Q, (CRR′)rC(O)NRa(CRR′)r—Q, (CRR′)r′NRaC(O) (CRR′)r—Q, (CRR′)r′OC(O)O(CRR′)r—Q, (CRR′)r′OC(O)NRa(CRR′)r—Q, (CRR′)r′NRaC(O)O(CRR′)r—Q, (CRR′)r′NRaC(O)NRa(CRR′)r—Q, (CRR′)r′S(O)p(CRR′)r—Q, (CRR′)r′SO2NRa(CRR′)r—Q, (CRR′)r′NRaSO2(CRR′)r—Q, (CRR′)r′NRaSO2NRa(CRR′)r—Q, (CRR′)r′NRaC(O) (CRR′)r″NHQ, (CRR′)r′NRaC(O)(CRR′)rNHC(O)ORa, and (CRR′)r′NRaC(O) (CRR′)rNHC(O) (CRR′)rNHC(O)ORa;
• Q is selected from H and a C3-13 carbocyclic residue substituted with 0-5 Rb;
• R4 is selected from H, C1-10 alkylene-H, C2-10 alkenylene-H, C2-10 alkynylene-H, (CRR′)r′O(CRR′)r—H, (CRR′)r′NRa(CRR′)r—H, (CRR′)r′C(O) (CRR′)r—H, (CRR′)r′C(O)O(CRR′)r—H, (CRR′)r′OC(O)(CRR′)r—H, (CRR′)r′C(O)NRa(CRR′)r—H, (CRR′)r′NRaC(O) (CRR′)r—H, (CRR′)r′OC(O)O(CRR′)r—H, (CRR′)r′OC(O)NRa(CRR′)r—H, (CRR′)r′NRaC(O)O(CRR′)r—H, (CRR′)r′NRaC(O)NRa(CRR′)r—H, (CRR′)r′S(O)p(CRR′)r—H, (CRR′)r′SO2NRa(CRR′)r—H, (CRR′)r′NRaSO2(CRR′)r—H, and (CRR′)r′NRaSO2NRa(CRR′)r—H;
• alternatively, R3 and R4 combine to form a C3-13 carbocyclic residue substituted with R1′ and 0-3 Rb;
• Ra, at each occurrence, is independently selected from H, C1-4 alkyl, phenyl and benzyl;
• Ra′, at each occurrence, is independently selected from H, C1-4 alkyl, phenyl and benzyl;
• Ra″, at each occurrence, is independently selected from H, C1-4 alkyl, benzyl, C3-7 carbocyclic residue, or a 5 to 6 membered heteroaromatic ring containing 1-4 heteroatoms selected from the group consisting of N, O, and S;
• alternatively, Ra and Ra′ taken together with the nitrogen to which they are attached form a 5 or 6 membered ring containing from 0-1 additional heteroatoms selected from the group consisting of N, O, and S;
• Rb, at each occurrence, is independently selected from C1-6 alkyl, ORa, Cl, F, Br, I, ═O, CN, NO2, NRaRa′, C(O)Ra″, C(O)ORa, C(O)NRaRa′, S(O)2NRaRa′, S(O)pRa, CF3, and CF2CF3;
• Rc, at each occurrence, is independently selected from C1-6 alkyl, ORa, Cl, F, Br, I, ═O, CN, NO2, NRaRa′, C(O)Ra, C(O)ORa, C(O)NRaRa′, NRaC(O)NRaRa′, S(O)2NRaRa′, S(O)pRa, CF3, CF2CF3, —CH(═NOH), —C(═NOH)CH3, (CRR′)sO(CRR′)s′Rd, (CRR′)sS(O)p(CRR′)s′Rd, (CRR′)sNRa(CRR′)s′Rd, phenyl, and a 5-14 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S;
• R5, at each occurrence, is selected from C1-10 alkyl substituted with 0-2 Rb, and C1-8 alkyl substituted with 0-2 Rd;
• Rd, at each occurrence, is independently selected from phenyl substituted with 0-3 Rb, biphenyl substituted with 0-2 Rb, and naphthyl substituted with 0-3 Rb;
• R6, at each occurrence, is selected from phenyl, naphthyl, C1-10 alkyl-phenyl-C1-6 alkyl-, C3-11 cycloalkyl, C1-6 alkylcarbonyloxy-C1-3 alkyl-, C1-6 alkoxycarbonyloxy-C1-3 alkyl-, C2-10 alkoxycarbonyl, C3-6 cycloalkylcarbonyloxy-C1-3 alkyl-, C3-6 cycloalkoxycarbonyloxy-C1-3 alkyl-, C3-6 cycloalkoxycarbonyl, phenoxycarbonyl, phenyloxycarbonyloxy-C1-3 alkyl-, phenylcarbonyloxy-C1-3 alkyl-, C1-6 alkoxy-C1-6 alkylcarbonyloxy-C1-3 alkyl-, —C1-10 alkyl-NR7R7a, —CH(R8)OC(═O)R9, and, —CH(R8)OC (═O)OR9;
• R7 is selected from H and C1-10 alkyl, C2-6 alkenyl, C3-6 cycloalkyl-C1-3 alkyl-, and phenyl-C1-6 alkyl-;
• R7a is selected from H and C1-10 alkyl, C2-6 alkenyl, C3-6 cycloalkyl-C1-3 alkyl-, and phenyl-C1-6 alkyl-;
• R8 is selected from H and C1-4 linear alkyl;
• R9 is selected from H, C1-8 alkyl substituted with 1-2 Re, C3-8 cycloalkyl substituted with 1-2 Re, and phenyl substituted with 0-2 Rb;
• Re, at each occurrence, is selected from C1-4 alkyl, C3-8 cycloalkyl, C1-5 alkoxy, phenyl substituted with 0-2 Rb;
• p, at each occurrence, is selected from 0, 1, and 2;
• r, at each occurrence, is selected from 0, 1, 2, 3, 4, and 5;
• r′, at each occurrence, is selected from 0, 1, 2, 3, 4, and 5;
• r″, at each occurrence, is selected from 1, 2, and 3;
• s, at each occurrence, is selected from 0, 1, 2 and 3;
• and,
• s′, at each occurrence, is selected from 0, 1, 2, and 3.