Inhibitors of cathepsin S

A compound having the Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• Q is a piperazinyl substituted with 0-2 RQ, wherein Q is connected to —C(═O)— via a ring nitrogen atom;
• each RQ is independently a member selected from the group consisting of OH, F, Cl, —S(═O)2CH3—, acetyl, ═O, C1-C6 alkyl, C1-C6 alkoxy, CF3, OCF3 and NR10R11;
• A is a member selected from the group consisting of —O—CR1R2—, —NH—CR1R2—, —CR3R4—O—, and —CR3R4—CR1R2—;
• each of R1 and R3 is independently a member selected from the group consisting of H, a C1-C6 alkoxy, a C1-C6 alkyl substituted with 0-2 R1a, 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, a C3-C6 alkynyl, a C3-C7 cycloalkyl substituted with 0-2 RQ, and a C7-C11 bicycloalkyl substituted with 0-2 RQ;
• phenyl substituted with 0-3 R13, 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 R13;
• each R1a is independently a member selected from the group consisting of a C6-C10 aryl substituted with 0-3 R13, 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 R13, a C3-C8 cycloalkyl substituted with 0-2 RQ, a C7-C11 bicycloalkyl substituted with 0-2 RQ, and a C1-C3 perfluoroalkyl;
• each of R2 and R4 is independently a member selected from the group consisting of H, F, OH, C1-C6 alkyl and C1-C6 alkoxy;
• R5 is a member selected from the group consisting of H, C(═O)OR14, C(═O)NR15R16 phenyl substituted with 0-2 R13, 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 0-2 R13, C3-C7 cycloalkyl, C1-C6 alkyl substituted with 0-2 R21, wherein said C1-C6 alkyl may optionally contain a heteroatom selected from the group consisting of —O—, —S—, —S(═O)—, —S(═O)2— and —NR22—;
• each of R6, R7, R8 and R9 is independently a member selected from the group consisting of H and C1-C6 alkyl;
• alternatively, R5 and R7 are taken together to form a C5-C7 cycloalkyl, wherein a methylene of said C5-C7 cycloalkyl may optionally be replaced with a heteroatom selected from the group of —O—, —S—, —S(═O)—, and —S(═O)2—;
• each R10 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 R11 is independently a member selected from the group consisting of H and C1-C4 alkyl;
• each R12 is independently a member selected from the group consisting of H, C3-C8 cycloalkyl, a phenyl substituted with 0-3 R13, 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 R13, and a C1-C6 alkyl substituted with 0-1 R19;
• each R13 is independently a member selected from the group consisting of H, OH, F, Cl, Br, CN, NO2, COOR17, C(═O)NR17R18, S(═O)2NR17R18, acetyl, —SCH3, —S(═O)CH3, —S(═O)2CH3, —NR10R11, C1-C6 alkoxy, C1-C3 perfluoroalkyl, C1-C3 perfluoroalkoxy and a C1-C6 alkyl;
• each R14 is independently a member selected from the group consisting of H, C3-C7 cycloalkyl, C1-C4 alkyl substituted with 0-1 R19, and a phenyl substituted with 0-3 R13;
• each R15 is independently a member selected from the group consisting of H, C3-C8 cycloalkyl, a phenyl substituted with 0-3 R13, and a C1-C6 alkyl substituted with 0-1 R19;
• each R16 is independently a member selected from the group consisting of H and C1-C4 alkyl;
• alternatively, R15 and R16 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 of R17 and R18 is independently a member selected from the group consisting of H, C1-C4 alkyl and C3-C6 cycloalkyl;
• each R19 is independently a member selected from the group consisting of H, C3-C7 cycloalkyl, a phenyl substituted with 0-3 R13 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 R13;
• Ar is a member selected from the group consisting of phenyl substituted with 0-3 R20, and a 5- to 10-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 R20;
• each R20 is independently a member selected from the group consisting of H, F, Cl, Br, CN, OR12, SCH3, S(═O)CH3, S(═O)2CH3, S(═O)2NR17R18, NR10R11, acetyl, —S(═O)2NH(C═O)CH3, C(═O)NR17R18, CO2R17, C(═NH)NH2, C1-C6 alkyl, CF3, OCF3 and OCF2H;
• alternatively, R20 and R9 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;
• wherein said 5- to 7-membered heterocyclic ring may be optionally substituted with 0-2 R24;
• each R21 is independently a member selected from the group consisting of H, OH, F, Cl, CN, NO2, C(═O)OR14, C(═O)NR15R16, NR22R23, C1-C3 perfluoroalkoxy, C1-C4 alkoxy, C2-C4 alkenyl, C2-C4 alkynyl, phenyl substituted with 0-3 R13, 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 R13, 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 R13 and is saturated or partially unsaturated, and C3-C8 cycloalkyl;
• R22 is independently a member selected from the group consisting of H, tBOC, Cbz, C3-C8 cycloalkyl, (C1-C6 alkyl)-C(═O)—, (C1-C6 alkyl)-S(═O)2—, a C1-C6 alkyl substituted with 0-1 R19, a phenyl substituted with 0-3 R13 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 R13;
• each R23 is independently a member selected from the group consisting of H and C1-C4 alkyl;
• each R24 is independently a member selected from the group consisting of C1-C4 alkyl, F, Cl and C1-C4 alkoxy, CF3 and OCF3;
• alternatively, two R24 may be combined to form C3-C6 cycloalkyl.