Spiro-cyclic β-amino acid derivatives as inhibitors of matrix metalloproteases and TNF-α converting enzyme (TACE)

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, —N(OH)COR5, —N(OH)CHO, —SH, —CH2SH, —S(O)(═NH)Ra, —SN2H2Ra, —PO(OH)2, and —PO(OH)NHRa;
• ring B is a 5 membered non-aromatic carbocycle;
• ring C forms a spiro ring on Ring B and is a 5 membered heterocycle consisting of:
• carbon atoms, 0-1 carbonyl group, 0-1 double bond, and 1 ring heteroatoms selected from O, N, NR2, and S(O)p and substituted with 0-6 Re;
• Z is phenyl substituted with 0-4 Rb;
• Ua is absent or is O;
• Xa is absent or is C1-3 alkylene;
• Ya is absent;
• Za is selected from pyridinyl substituted with 0-3 Rc and quinolinyl substituted with 0-5 Rc;
• R1 is selected from H, C1-4 alkyl, phenyl, and benzyl;
• R2 is selected from Q, Cl, F, (C1-10 alkylene substituted with 0-3 Rb1)—Q, (C2-10 alkenylene substituted with 0-3 Rb1)—Q, (C2-10 alkynylene substituted with 0-3 Rb1)—Q, (CRaRa1)r1O(CRaRa1)r—Q, (CRaRa1)r1NRa(CRaRa1)r—Q, (CRaRa1)r1C(O)(CRaRa1)r—Q, (CRaRa1)r1C(O)O(CRaRa1)r—Q, (CRaRa1)r1C(O)O—C2-5 alkenylene, (CRaRa1)r1C(O)O—C2-5 alkynylene, (CRaRa1)r1OC(O)(CRaRa1)r—Q, (CRaRa1)r1C(O)NRaRa1, (CRaRa1)r1C(O)NRa(CRaRa1)r—Q, (CRaRa1)r1NRaC(O)(CRaRa1)r—Q, (CRaRa1)r1OC(O)O(CRaRa1)r—Q, (CRaRa1)r1OC(O)NRa(CRaRa1)r—Q, (CRaRa1)r1NRaC(O)O(CRaRa1)r—Q, (CRaRa1)r1NRaC(O)NRa(CRaRa1)r—Q, (CRaRa1)r1S(O)p(CRaRa1)r—Q, (CRaRa1)r1SO2NRa(CRaRa1)r—Q, (CRaRa1)r1NRaSO2(CRaRa1)r—Q, and (CRaRa1)r1NRaSO2NRa(CRaRa1)r—Q;
• R2a is selected from H, C1-6 alkyl, ORa, NRaRa1, and S(O)pRa;
• R2b is H or C1-6 alkyl;
• Q is selected from H and a C3-13 carbocycle substituted with 0-5 Rd;
• R3 is selected from Q1, Cl, F, C1-6 alkylene-Q1, C2-6 alkenylene-Q1, C2-6 alkynylene-Q1, (CRaRa1)r1O(CRaRa1)r—Q1, (CRaRa1)r1NRa(CRaRa1)r—Q1, (CRaRa1)r1NRaC(O)(CRaRa1)r—Q1, (CRaRa1)r1C(O)NRa(CRaRa1)r—Q1, (CRaRa1)r1C(O)(CRaRa1)r—Q1, (CRaRa1)r1C(O)O(CRaRa1)r—Q1, (CRaRa12)r1S(O)p(CRaRa1)r—Q1, and (CRaRa1)r1SO2NRa(CRaRa1)r—Q1;
• Q1 is selected from H and phenyl substituted with 0-3 Rd;
• Ra, at each occurrence, is independently selected from H, C1-4 alkyl, phenyl and benzyl;
• Ra1, at each occurrence, is independently selected from H and C1-4 alkyl;
• Ra2, at each occurrence, is independently selected from C1-4 alkyl, phenyl and benzyl;
• Rb, at each occurrence, is independently selected from C1-6 alkyl, ORa, Cl, F, Br, I, ═O, —CN, NO2, NRaRa1, C(O)Ra, C(O)ORa, C(O)NRaRa1, RaNC(O)NRaRa1, OC(O)NRaRa1, RaNC(O)ORa, S(O)2NRaRa1, NRaS(O)2Ra2, NRaS(O)2NRaRa1, OS(O)2NRaRa1, NRaS(O)2Ra2, S(O)pRa2, CF3, and CF2CF3;
• Rb1, at each occurrence, is independently selected from ORa, Cl, F, Br, I, ═O, —CN, NO2, and NRaRa1;
• Rc, at each occurrence, is independently selected from C1-6 alkyl, ORa, Cl, F, Br, I, ═O, —CN, NO2, NRaRa1, C(O)Ra, C(O)ORa, C(O)NRaRa1, RaNC(O)NRaRa1, OC(O)NRaRa1, RaNC(O)ORa, S(O)2NRaRa1, NRaS(O)2Ra2, NRaS(O)2NRaRa1, OS(O)2NRaRa1, NRaS(O)2Ra2, S(O)pRa2, CF3, CF2CF3, CH2F, CHF2, CF2CH3, C(CH3)2F, OCF3, and C3-10 carbocycle substituted with 0-3 Rc1;
• Rc1, at each occurrence, is independently selected from C1-6 alkyl, ORa, Cl, F, Br, I, ═O, —CN, NO2, NRaRa1, C(O)Ra, C(O)ORa, C(O)NRaRa1, RaNC(O)NRaRa1, OC(O)NRaRa1, RaNC(O)ORa, S(O)2NRaRa1, NRaS(O)2Ra2, NRaS(O)2NRaRa1, OS(O)2NRaRa1, NRaS(O)2Ra2, S(O)pRa2, CF3, CF2CF3, CH2F, and CHF2;
• Rd, at each occurrence, is independently selected from C1-6 alkyl, ORa, Cl, F, Br, I, ═O, —CN, NO2, NRaRa1, C(O)Ra, C(O)ORa, C(O)NRaRa1, RaNC(O)NRaRa1, OC(O)NRaRa1, RaNC(O)ORa, S(O)2NRaRa1, NRaS(O)2Ra2, NRaS(O)2NRaRa1, OS(O)2NRaRa1, NRaS(O)2Ra2, S(O)pRa2, CF3, CF2CF3, and C3-10 carbocycle;
• Re, at each occurrence, is independently selected from C1-6 alkyl, ORa, Cl, F, Br, I, ═O, —CN, NO2, NRaRa1, C(O)Ra, C(O)ORa, C(O)NRaRa1, RaNC(O)NRaRa1, OC(O)NRaRa1, RaNC(O)ORa, S(O)2NRaRa1, NRaS(O)2Ra2, NRaS(O)2NRaRa1, OS(O)2NRaRa1, NRaS(O)2Ra2, S(O)pRa2, CF3, CF2CF3, C3-10 carbocycle substituted with 0-2 Rc1, and (CRaRa1)r1-C3-10 carbocycle substituted with 0-2 Rc1;
• R5, at each occurrence, is selected from C1-10 alkyl substituted with 0-2 Rb and C1-8 alkyl substituted with 0-2 Rf;
• Rf, at each occurrence, is selected from phenyl substituted with 0-2 Rb and biphenyl substituted with 0-2 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 Rg, C3-8 cycloalkyl substituted with 1-2 Rg, and phenyl substituted with 0-2 Rb;
• Rg, at each occurrence, is selected from C1-4 alkyl, C3-8 cycloalkyl, C1-5 alkoxy, and 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, and 4;
• and
• r1, at each occurrence, is selected from 0, 1, 2, 3, and 4.