Inhibitors of cathepsin S

A compound having the Formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• A is —CH2—, —CH2CH2— or a bond;
• R1 is a benzimidazolyl substituted with 0-3 R1a or a C3-C8 heterocycle containing 1 to 2 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein said heterocycle is substituted with 0-2 R 1a;
• each R1a is independently a member selected from the group consisting of F, Cl, Br, CN, NO2, OH, acetyl, C(═O)OR10, C(═O)NR10R11, S(═O)2NR10R11;
• C3-C7 cycloalkyl;
• —SCH3, —S(═O)CH3, —S(═O)2CH3, NR12R13, C1-C6 alkoxy, C1-C3 perfluoroalkyl, C1-C3 perfluoroalkoxy, a C1-C6 alkyl, phenyl substituted with 0-3 R4, a 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein said heteroaryl is substituted with 0-3 R4, a C3-C8 heterocycle containing 1 to 2 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein said heterocycle is substituted with 0-2 R4 and is saturated or partially unsaturated;
• R2 is a member selected from the group consisting of a C1-C6 alkyl substituted with 0-2 R2a, wherein said C1-C6 alkyl may optionally contain a heteroatom selected from the group consisting of —O—, —S—, —S(═O)— and —S(═O)2—, a C2-C6 alkenyl substituted with 0-1 R2a, a C3-C6 alkynyl substituted with 0-1 R2a, a C3-C7 cycloalkyl substituted with 0-2 R2b, a C7-C11 bicycloalkyl substituted with 0-2 R2b, phenyl substituted with 0-3 R14, a 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein said heteroaryl is substituted with 0-3 R14;
• each R2a is independently a member selected from the group consisting of a C6-C10 aryl substituted with 0-3 R14, a perfluorophenyl, a C3-C8 cycloalkyl substituted with 0-2 R2b, a C7-C11 bicycloalkyl substituted with 0-2 R2b, and a 5- to 6-membered monocyclic or 8- to 10-membered bicyclic heteroaryl containing 1 to 4 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein said heteroaryl is substituted with 0-3 R14;
• each R2b is independently a member selected from the group consisting of H, OH, F, Cl, C1-C6 alkyl, C1-C6 alkoxy, CF3, and OCF3;
• R3 is a member selected from the group consisting of H and C1-C6 alkyl;
• R4 is a member selected from the group consisting of H, C(═O)OR15, C(═O)NR16R17, phenyl substituted with 0-2 R14, 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein said heteroaryl is substituted with 0-2 R14, C3-C7 cycloalkyl, C1-C6 alkyl substituted with 0-2 R20, wherein said C1-C6 alkyl may optionally contain a heteroatom selected from the group consisting of —O—, —S—, —S(═O)—, —S(═O)2— and —NR6—;
• each of R5, R6, R7 and R8 is independently a member selected from the group consisting of H and C1-C6 alkyl;
• alternatively, R4 and R6 are taken together to form a C5-C7 cycloalkyl;
• each of R10 and R11 is independently a member selected from the group consisting of H, and C1-C4 alkyl;
• alternatively, R10 and R11 on the same nitrogen are taken together to form a 5- to 7-membered heterocyclic ring containing 1-2 heteroatoms each independently a member selected from the group consisting of N, O and S;
• each R12 is independently a member selected from the group consisting of H, C1-C4 alkyl, (C1-C4 alkyl)-C(═O)— and (C1-C4 alkyl)-S(═O)2—;
• each R13 independently a member selected from the group consisting of H and C1-C4 alkyl;
• alternatively, R12 and R13 on the same nitrogen are taken together to form a 5- to 7-membered heterocyclic ring containing 1-2 heteroatoms each independently a member selected from the group consisting of N, O and S;
• each R14 independently a member selected from the group consisting of H, OH, F, Cl, Br, CN, NO2, COOR10, C(═O)NR10R11, S(═O)2NR10R11, acetyl, —SCH3, —S(═O)CH3, —S(═O)2CH3, NR12R13, C1-C6 alkoxy, C1-C3 perfluoroalkyl, C1-C3 perfluoroalkoxy, and a C1-C6 alkyl;
• each R15 is independently a member selected from the group consisting of H, C3-C7 cycloalkyl, C1-C4 alkyl substituted with 0-1 R18, and a phenyl substituted with 0-3R14;
• each R16 is independently a member selected from the group consisting of H, C3-C8 cycloalkyl, a phenyl substituted with 0-3 R14, and a C1-C6 alkyl substituted with 0-1 R18;
• each R17 is independently a member selected from the group consisting of H and C1-C4 alkyl;
• alternatively, R16 and R17 on the same N atom are taken together to form a C5-C7 heterocycle containing 1-2 heteroatoms each independently a member selected from the group consisting of N, O and S.
• each R18 is independently a member selected from the group consisting of H, C3-C7 cycloalkyl, a phenyl substituted with 0-3 R14 and a 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein said 5- to 6-membered heteroaryl is substituted with 0-3 R14;
• each R19 is independently a member selected from the group consisting of H, F, Cl, Br, CN, OR21, SCH3, S(═O)CH3, S(═O)2CH3, S(═O)2NR10R11, NR12R13, acetyl, C(═O)NR10R11, CO2R10, C(═NH)NH2, C1-C6 alkyl, CF3;
• and a 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein said heteroaryl is substituted with 0-3 R14;
• alternatively, R19 and R8 are taken together to form a 5- to 7-membered heterocyclic ring containing 1-2 heteroatoms, each independently a member selected from the group consisting of N, O and S, wherein said 5 to 7 membered heterocyclic ring is ortho-fused to Ar and wherein said 5- to 7-membered heterocyclic ring may be optionally substituted with 0-2 R22;
• each R20 is independently a member selected from the group consisting of H, OH, F, Cl, CN, NO2, C(═O)OR15, C(═O)NR16R17, NR12R13, C1-C3 perfluoroalkoxy, C1-C3 perfluoroalkyl, C1-C4 alkoxy, C2-C4 alkenyl, C2-C4 alkynyl, phenyl substituted with 0-3 R14, 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein said heteroaryl is substituted with 0-3 R4, C3-C8 heterocycle containing 1 to 2 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein said heterocycle is substituted with 0-2 R14 and is saturated or partially unsaturated, and C3-C8 cycloalkyl;
• each R21 is independently a member selected from the group consisting of H, CF3, CHF2, C1-C6 alkyl, C3-C8 cycloalkyl, a phenyl substituted with 0-3 R14, a 5- to 6-memebered heteroaryl containing 1 to 4 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein said 5- to 6-membered heteroaryl is substituted with 0-3 R14, and a CH2 substituted with 1 R18;
• and
• each R22 is independently a member selected from the group consisting of C1-C4 alkyl, F, Cl and C1-C4 alkoxy, CF3 and OCF3, or alternatively, two R22 may be combined to form C3-C6 cycloalkyl.