US2008242671A1PendingUtilityA1
Inhibitors of cathepsin s
Est. expiryMar 24, 2023(expired)· nominal 20-yr term from priority
Inventors:Hong LiuPhillip AlperArnab K. ChatterjeeDavid C. TullyBadry BursulayaDavid H. WoodmanseeRobert EppleJennifer HarrisJun Li
C07D 405/12C07C 237/22C07C 237/24C07C 257/18C07C 311/19C07C 311/29C07D 207/12C07D 207/24C07D 209/08C07D 209/42C07D 211/60C07D 213/71C07D 231/14C07D 257/04C07D 261/18C07D 271/10C07D 307/20C07D 307/24C07D 307/68C07D 309/08C07D 311/22C07D 333/40C07D 335/02C07D 401/12C07D 401/14C07D 403/06C07D 403/12C07D 405/14C07D 409/12C07D 409/14C07D 413/06C07D 413/12C07D 413/14C07D 417/12C07D 417/14C07C 2601/14
59
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Claims
Abstract
The present invention provides compounds, compositions and methods for the selective inhibition of cathepsin S. In a preferred aspect, cathepsin S is selectively inhibited in the presence of at least one other cathepsin isozyme. The present invention also provides methods for treating a disease state in a subject by selectively inhibiting cathepsin S.
Claims
exact text as granted — not AI-modified1 . A compound of Formula I:
or a pharmaceutically acceptable salt or prodrug thereof,
wherein:
R 1 is a member selected from the group consisting of H, C 6 -C 10 aryl substituted with 0-3 R 1a , 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 R 1a , a C 3 -C 8 cycloalkyl substituted with 0-2 R 1b , wherein said C 3 -C 8 cycloalkyl is saturated or unsaturated; and a C 3 -C 8 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 1c and is saturated or unsaturated;
each R 1a is independently a member selected from the group consisting of H, C 1 -C 3 perfluoroalkyl, C 3 -C 7 cycloalkyl, F, Cl, Br, CN, NO 2 , OR 10 , SCH 3 , S(═O)CH 3 , S(═O) 2 R 10 , NR 11 R 12 , acetyl, C(═O)OR 13 , C(═O)NR 13 R 14 , S(═O) 2 NR 13 R 14 , phenyl substituted with 0-3 R 15 , a 5- to 6-membered monocyclic 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 R 15 , a C 3 -C 8 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 1c and is saturated or unsaturated, and a C 1 -C 4 alkyl substituted with 0-2 R 16 ;
each R 1b is independently a member selected from the group consisting of H, OH, F, Cl, acetyl, ═O, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, CF 3 and OCF 3 ;
each R 1c is independently a member selected from the group consisting of H, OH, F, Cl, ═O, C 1 -C 6 alkyl substituted with 0-2 R 16 , C 1 -C 6 alkoxy, CF 3 , OCF 3 , C(═O)R 10 , S(═O) 2 R 10 , tBoc, Cbz; phenyl substituted with 0-3 R 15 ; a 5- to 6-membered monocyclic 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 R 15 ;
R 2 is a member selected from the group consisting of a phenyl substituted with 0-3 R 15 , a 5- to 6-membered monocyclic 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 R 15 , a C 1 -C 6 alkyl substituted with 0-2 R 2a , wherein said C 1 -C 6 alkyl optionally contains a heteroatom selected from the group consisting of —O—, —S—, and —S(═O) 2 —, a C 2 -C 6 alkenyl, a C 2 -C 6 alkynyl, a C 3 -C 7 cycloalkyl substituted with 0-2 R 19 , wherein said C 3 -C 7 cycloalkyl optionally contains a heteroatom selected from —O—, —S—, and —S(═O) 2 —, and a C 7 -C 11 bicycloalkyl substituted with 0-2 R 19 ;
each R 2a is independently a member selected from the group consisting of a C 6 -C 10 aryl substituted with 0-3 R 15 , 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 R 15 , a C 3 -C 8 cycloalkyl substituted with 0-2 R 19 , and a C 7 -C 11 bicycloalkyl substituted with 0-2 R 19 ;
R 3 is a member selected from the group consisting of H and C 1 -C 4 alkyl;
subscript n is 0 or 1;
R 4 is a member selected from the group consisting of H and C 1 -C 6 alkyl;
alternatively, R 2 and R 4 are taken together to form a C 5 -C 7 cycloalkyl substituted with 0-2 R 19 ;
R 5 is a member selected from the group consisting of H, C 3 -C 7 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkyne, phenyl substituted with 0-2 R 15 ; 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 R 15 , a C 1 -C 6 alkyl substituted with 0-2 R 18 , wherein said C 1 -C 6 alkyl optionally contains a heteroatom selected from the group consisting of —O—, —S—, —S(═O)—, —S(═O) 2 — and —NR 17 —;
Y is a member independently selected from the group consisting of a bond and —(CR 20 R 21 ) m —W—(CR 22 R 23 ) p —;
subscript p is 1 or 2;
subscript m is 0 or 1;
W is a member independently selected from the group consisting of a bond, —O—, —S—, —S(═O)—, —S(═O) 2 — and —NR 12 —;
X is selected from the group consisting of —C(═O)—, —OC(═O)—, —NR 24 C(═O)— and —S(═O) 2 —;
each of R 6 , R 7 , R 8 and R 9 is independently a member selected from the group consisting of H and C 1 -C 4 alkyl;
alternatively, R 5 and R 7 are taken together to form a C 5 -C 7 cycloalkyl substituted with 0-2 R 19 ;
alternatively, R 5 and R 9 are taken together to form a 6-7 membered heterocyclic ring containing 1-2 heteroatoms each independently a member selected from the group consisting of N, O and S;
Ar is a member selected from the group consisting of phenyl substituted with 0-3 R 29 ; and 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 R 29 ;
each R 10 is independently a member selected from the group consisting of H, C 3 -C 7 cycloalkyl, a C 1 -C 3 perfluoroalkyl, a C 1 -C 4 alkyl substituted with 0-1 R 25 , a phenyl substituted with 0-3 R 15 ; 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 R , and a C 3 -C 8 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 1c ;
each R 11 is independently a member selected from the group consisting of H, t BOC, Cbz, C 3 -C 8 cycloalkyl, (C 1 -C 6 alkyl)-C(═O)—, (C 1 -C 6 alkyl)-S(═O) 2 — and a C 1 -C 6 alkyl;
each of R 12 , R 13 and R 14 is independently a member selected from the group consisting of H and C 1 -C 4 alkyl;
alternatively, R 13 and R 14 on the same N atom are taken together to form a C 5 -C 7 heterocycle containing 1-2 heteroatoms each independently a member selected from the group consisting of N, O and S;
each R 15 is independently a member selected from the group consisting of H, OH, F, Cl, Br, I, CN, NO 2 , COOR 13 , C(═O)NR 13 R 14 , S(═O) 2 NR 13 R 14 , acetyl, —SCH 3 , —S(═O)CH 3 , —S(═O) 2 CH 3 , NR 26 R 27 , C 1 -C 6 alkoxy, C 1 -C 3 perfluoroalkyl, C 1 -C 3 perfluoroalkoxy and a C 1 -C 6 alkyl;
each R 16 is independently a member selected from the group consisting of H, OH, COOR 13 , C(═O)NR 13 R 14 , S(═O) 2 NR 13 R 14 , acetyl, —SCH 3 , —S(═O)CH 3 , —S(═O) 2 CH 3 , C 1 -C 6 alkoxy, NR 26 R 27 , a phenyl substituted with 0-3 R 15 , 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 R 15 , and a C 3 -C 8 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 15 and is saturated or unsaturated;
R 17 is a member selected from the group consisting of H and C 1 -C 4 alkyl;
each R 18 is independently a member selected from the group consisting of H, OH, F, Cl, CN, NO 2 , C(═O)OR 30 , C(═O)NR 13 R 14 , NR 11 R 12 , a C 1 -C 3 perfluoroalkyl, a C 1 -C 3 perfluoroalkoxy, a phenyl substituted with 0-3 R 15 , 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 R 15 , a C 3 -C 8 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 15 and is saturated or unsaturated; and C 3 -C 8 cycloalkyl;
each R 19 is a independently a member selected from the group consisting of C 1 -C 4 alkyl, F, Cl and C 1 -C 4 alkoxy, CF 3 and OCF 3 ;
alternatively, two R 19 on the same carbon may be combined to form C 3 -C 6 cycloalkyl;
each of R 20 , R 21 , R 22 and R 23 is independently a member selected from the group consisting of a bond, H, F, OH, C 1 -C 4 alkyl, and C 1 -C 3 alkylhydroxy;
alternatively, R 20 and R 21 or R 22 and R 23 are taken together to form a C 3 -C 6 cycloalkyl;
R 24 is a member selected from the group consisting of H and C 1 -C 4 alkyl;
each R 25 is independently a member selected from the group consisting of H, C 3 -C 7 cycloalkyl, a phenyl substituted with 0-3 R 15 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 0-2 R 15 ;
each R 26 is independently a member selected from the group consisting of H, C 1 -C 4 alkyl, (C 1 -C 4 alkyl)-C(═O)— and (C 1 -C 4 alkyl)-S(═O) 2 —;
each R 27 is independently a member selected from the group consisting of H and C 1 -C 4 alkyl;
alternatively, R 26 and R 27 on the same N atom are taken together to form a C 5 -C 7 heterocycle containing 1-2 heteroatoms each independently a member selected from the group consisting of N, O and S;
each R 28 is independently a member selected from the group consisting of H, a C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, a phenyl substituted with 0-3 R 15 , a benzyl substituted with 0-2 R 15 ;
each R 29 is independently a member selected from the group consisting of H, F, Cl, Br, I, CN, NO 2 , OR 28 , SR 28 , S(═O)R 28 , S(═O) 2 R 28 , S(═O) 2 NR 13 R 14 , NR 26 R 27 , acetyl, C(═O)NR 13 R 14 , C(═O)OR 13 , C 1 -C 6 alkyl, OCHF 2 , SCF 3 , OCF 3 , —C(═NH)NH 2 , and 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently a member selected from the group consisting of N, O and S;
alternatively, two R 29 substituted on adjacent atoms may be combined to form a 5 to 6 membered heterocyclic fused radical, wherein said 5 to 6 membered heterocyclic fused radical comprise 1 or 2 heteroatom(s) selected from O, S and N; wherein said 5 to 6 membered heterocyclic fused radical is substituted with 0-1 oxo;
alternatively, R 29 and R 9 are taken together to form a 5- to 7-membered fused heterocyclic ring containing 1-2 heteroatom(s) each independently a member selected from the group consisting of N, O and S; wherein said 5 to 7 membered fused heterocyclic ring is substituted with 0-2 R 19 ;
each R 30 is independently a member selected from the group consisting of H, C 3 -C 7 cycloalkyl, C 1 -C 4 alkyl substituted with 0-1 R 25 , a phenyl substituted with 0-3 R 15 , 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 R 15 ; and
with the proviso that R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are not all hydrogen.
2 . The compound of claim 1 , according to Formula Ia
wherein:
R 1 is 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 1 R 1a ;
R 1a is independently a member selected from the group consisting of phenyl substituted with 0-2 R 15 , and a 5- to 6-membered monocyclic 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 R 15 ;
R 2 is a member selected from the group consisting of a phenyl substituted with 0-3 R 15 , a 5- to 6-membered monocyclic 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 R 15 , a C 1 -C 6 alkyl, a C 1 -C 3 alkyl substituted with 1 R 2a , and a C 3 -C 7 cycloalkyl substituted with 0-2 R 19 ;
each R 2a is independently a member selected from the group consisting of a C 6 -C 10 aryl substituted with 0-3 R 15 , 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 R 15 , a C 3 -C 8 cycloalkyl substituted with 0-2 R 19 and a C 7 -C 11 bicycloalkyl substituted with 0-2 R 19 ; and
Ar is phenyl substituted with 0-3 R 29 , or alternatively, R 29 and R 9 are taken together to form a 5- to 7-membered fused heterocyclic ring containing 1-2 heteroatom(s) each independently a member selected from the group consisting of N, O and S; wherein said 5- to 7-membered fused heterocyclic ring is substituted with 0-2 R 19 .
3 . The compound of claim 2 , wherein said compound is of the formula:
4 . The compound of claim 1 , wherein:
R 1 is a member selected from the group consisting of phenyl substituted with 0-3 R 1a , furanyl substituted with 0-3 R 1a , C 3 -C 6 cycloalkyl substituted with 0-3 R 1a , indolyl substituted with 0-3 R 1a , 5- or 6-membered heterocyclyl substituted with 0-3 R 1c , pyidazinyl substituted with 0-3 R 1a , imadazolyl substituted with 0-3 R 1a , thienyl substituted with 0-3 R 1a , thiazolyl substituted with 0-3 R 1a , oxadiazolyl substituted with 0-3 R 1a , pyrazolyl substituted with 0-3 R 1a , isoxazolyl substituted with 0-3 R 1a , tetrazolyl substituted with 0-3 R 1a , oxazolyl substituted with 0-3 R 1a and pyridyl substituted with 0-3 R 1a .
5 . The compound of claim 2 , according to Formula Ib:
wherein:
each R 15 , if present, is independently a member selected from the group consisting of OH, F, Cl, Br, I, CN, NO 2 , COOR 13 , C(═O)NR 13 R 14 , S(═O) 2 NR 13 R 14 , acetyl, —SCH 3 , —S(═O)CH 3 , —S(═O) 2 CH 3 , NR 26 R 27 , C 1 -C 6 alkoxy, C 1 -C 3 perfluoroalkyl, C 1 -C 3 perfluoroalkoxy and a C 1 -C 6 alkyl;
and
A is a 5-membered heteroaryl selected from the group consisting of furanylene, thienylene, thiazolylene, oxadiazolylene, isoxazolylene, tetrazolylene, and oxazolylene.
6 . The compound of claim 5 , wherein:
R 2 is a member selected from the group consisting of a C 1 -C 2 alkyl substituted with 1 R 2a , and C 1 -C 6 alkyl; each R 2a is independently a member selected from the group consisting of a phenyl substituted with 0-3 R 15 , and a C 3 -C 8 cycloalkyl substituted with 0-2 R 19 ; R 5 is a member selected from the group consisting of H, C 3 -C 7 cycloalkyl; a C 1 -C 6 alkyl substituted with 0-1 R 18 , wherein said C 1 -C 6 alkyl optionally contains a heteroatom selected from the group consisting of —O—, —S—, —S(═O)—, —S(═O) 2 — and —NR 17 —; and each R 18 is independently a member selected from the group consisting of H, OH, F, Cl, CN, C(═O)OR 30 , C(═O)NR 13 R 14 , NR 11 R 12 , a phenyl substituted with 0-3 R 15 , a C 3 -C 8 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 15 and is saturated or unsaturated; and C 3 -C 8 cycloalkyl.
7 . The compound of claim 1 , according to Formula Ia
wherein:
R 1 is a member selected from the group consisting of a C 3 -C 8 cycloalkyl substituted with 0-2 R 1b , wherein said C 3 -C 8 cycloalkyl is saturated or unsaturated and a C 4 -C 7 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 1c and is saturated or unsaturated;
R 2 is a member selected from the group consisting of a phenyl substituted with 0-3 R 15 , a 5- to 6-membered monocyclic 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 R 15 , a C 1 -C 6 alkyl substituted with 0-2 R 2a , and a C 3 -C 7 cycloalkyl substituted with 0-2 R 19 ; and
Ar is phenyl substituted with 0-3 R 29 , or alternatively, R 29 and R 9 are taken together to form a 5- to 7-membered fused heterocyclic ring containing 1-2 heteroatom(s) each independently a member selected from the group consisting of N, O and S; wherein said 5- to 7-membered fused heterocyclic ring is substituted with 0-2 R 19 .
8 . The compound of claim 7 , wherein:
R 2 is a member selected from the group consisting of a C 1 -C 2 alkyl substituted with 1 R 2a , and C 1 -C 6 alkyl; each R 2a is independently a member selected from the group consisting of a phenyl substituted with 0-3 R 15 , and a C 3 -C 8 cycloalkyl substituted with 0-2 R 19 ; R 5 is a member selected from the group consisting of H, C 3 -C 7 cycloalkyl; a C 1 -C 6 alkyl substituted with 0-1 R 18 , wherein said C 1 -C 6 alkyl optionally contains a heteroatom selected from the group consisting of —O—, —S—, —S(═O)—, —S(═O) 2 — and —NR 17 —; and each R 18 is independently a member selected from the group consisting of H, OH, F, Cl, CN, C(═O)OR 30 , C(═O)NR 13 R 14 , NR 11 R 12 , a phenyl substituted with 0-3 R 15 , a C 3 -C 8 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 15 and is saturated or unsaturated; and C 3 -C 8 cycloalkyl.
9 . The compound of claim 7 , wherein said compound is of the formula:
10 . The compound of claim 1 , according to Formula Ic
wherein:
R 1 is a member selected from the group consisting of tBu, phenyl substituted with 0-2 R 15 , 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 R 15 , and a C 4 -C 7 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 1c ;
each R 1c is independently a member selected from the group consisting of H, OH, F, Cl, ═O, C 1 -C 6 alkyl substituted with 0-2 R 16 , a C 1 -C 6 alkoxy, CF 3 , OCF 3 , C(═O)R 10 , S(═O) 2 R 10 , tBoc, Cbz, phenyl substituted with 0-3 R 5 , and a 5- to 6-membered monocyclic 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 R 15 ;
Y is a member independently selected from the group consisting of a bond and —(CR 20 R 21 ) m —W—(CR 22 R 23 ) p —, wherein m is 0, W is a bond, and R 22 R 23 are both H;
R 2 is a member selected from the group consisting of a phenyl substituted with 0-3 R 15 , a 5- to 6-membered monocyclic 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 R 15 , a C 1 -C 6 alkyl, a C 1 -C 3 alkyl substituted with 1 R 2a , and a C 3 -C 7 cycloalkyl substituted with 0-2 R 19 ;
each R 2a is independently a member selected from the group consisting of a C 6 -C 10 aryl substituted with 0-3 R 15 , 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 R 15 , a C 3 -C 8 cycloalkyl substituted with 0-2 R 19 , and a C 7 -C 11 bicycloalkyl substituted with 0-2 R 19 ; and
Ar is phenyl substituted with 0-3 R 29 , or alternatively, R 29 and R 9 are taken together to form a 5- to 7-membered fused heterocyclic ring containing 1-2 heteroatom(s) each independently a member selected from the group consisting of N, O and S; wherein said 5- to 7-membered fused heterocyclic ring is substituted with 0-2 R 19 .
11 . The compound of claim 10 , wherein:
R 2 is a member selected from the group consisting of a C 1 -C 2 alkyl substituted with 1 R 2a , and C 1 -C 6 alkyl; each R 2a is independently a member selected from the group consisting of a phenyl substituted with 0-3 R 15 , and a C 3 -C 8 cycloalkyl substituted with 0-2 R 19 ; R 5 is a member selected from the group consisting of H, C 3 -C 7 cycloalkyl; a C 1 -C 6 alkyl substituted with 0-1 R 18 , wherein said C 1 -C 6 alkyl optionally contains a heteroatom selected from the group consisting of —O—, —S—, —S(═O)—, —S(═O) 2 — and —NR 17 —; and each R 18 is independently a member selected from the group consisting of H, OH, F, Cl, CN, C(═O)OR 30 , C(═O)NR 13 R 14 , NR 11 R 12 , a phenyl substituted with 0-3 R 15 , a C 3 -C 8 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 15 and is saturated or unsaturated; and C 3 -C 8 cycloalkyl.
12 . The compound of claim 10 , wherein said compound is of the Formula:
13 . The compound of claim 1 , according to Formula Id
wherein:
R 1 is a member selected from the group consisting of methyl, benzyl, C 6 -C 10 aryl substituted with 0-3 R 13 , 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 R 1a ;
each R 1a is independently a member selected from the group consisting of H, C 1 -C 3 perfluoroalkyl, C 3 -C 7 cycloalkyl, F, Cl, Br, CN, NO 2 , OR 10 , SCH 3 , S(═O)CH 3 , S(═O) 2 R 10 , NR 11 R 12 , acetyl, C(═O)OR 13 , C(═O)NR 13 R 14 , S(═O) 2 NR 13 R 14 , phenyl substituted with 0-3 R 15 , a 5- to 6-membered monocyclic 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 R 15 ; and a C 1 -C 4 alkyl; and
Ar is phenyl substituted with 0-3 R 29 , or alternatively, R 29 and R 9 are taken together to form a 5- to 7-membered fused heterocyclic ring containing 1-2 heteroatom(s) each independently a member selected from the group consisting of N, O and S; wherein said 5- to 7-membered fused heterocyclic ring is substituted with 0-2 R 19 .
14 . The compound of claim 13 , wherein:
R 2 is a member selected from the group consisting of a C 1 -C 2 alkyl substituted with 1 R 2a , and C 1 -C 6 alkyl; each R 2a is independently a member selected from the group consisting of a phenyl substituted with 0-3 R 15 , and a C 3 -C 8 cycloalkyl substituted with 0-2 R 19 ; R 5 is a member selected from the group consisting of H, C 3 -C 7 cycloalkyl; a C 1 -C 6 alkyl substituted with 0-1 R 18 , wherein said C 1 -C 6 alkyl optionally contains a heteroatom selected from the group consisting of —O—, —S—, —S(═O)—, —S(═O) 2 — and —NR 17 —; and each R 18 is independently a member selected from the group consisting of H, OH, F, Cl, CN, C(═O)OR 30 , C(═O)NR 13 R 14 , NR 11 R 12 , a phenyl substituted with 0-3 R 15 , a C 3 -C 8 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 15 and is saturated or unsaturated; and C 3 -C 8 cycloalkyl.
15 . The compound of claim 13 , wherein said compound is of the Formula:
16 . The compound of claim 1 , according to Formula Ie
wherein:
R 1 is a member selected from the group consisting of a C 6 -C 10 aryl substituted with 0-3 R 1a , 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 R 1a ;
each R 1a is independently a member selected from the group consisting of H, C 1 -C 3 perfluoroalkyl, C 3 -C 7 cycloalkyl, F, Cl, Br, CN, NO 2 , OR 10 , SCH 3 , S(═O)CH 3 , S(═O) 2 R 10 , NR 11 R 12 , acetyl, C(═O)OR 13 , C(═O)NR 13 R 14 , S(═O) 2 NR 13 R 14 , phenyl substituted with 0-3 R 15 , a 5- to 6-membered monocyclic 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 R 15 , a C 3 -C 8 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 1c and is saturated or unsaturated, and a C 1 -C 4 alkyl substituted with 0-2 R 16 ; and
Ar is phenyl substituted with 0-3 R 29 , or alternatively, R 29 and R 9 are taken together to form a 5- to 7-membered fused heterocyclic ring containing 1-2 heteroatom(s) each independently a member selected from the group consisting of N, O and S; wherein said 5- to 7-membered fused heterocyclic ring is substituted with 0-2 R 19 .
17 . The compound of claim 16 , wherein:
R 2 is a member selected from the group consisting of a C 1 -C 2 alkyl substituted with 1 R 2a , and C 1 -C 6 alkyl; each R 2a is independently a member selected from the group consisting of a phenyl substituted with 0-3 R 15 , and a C 3 -C 8 cycloalkyl substituted with 0-2 R 19 ; and R 5 is a member selected from the group consisting of H, C 3 -C 7 cycloalkyl; a C 1 -C 6 alkyl, wherein said C 1 -C 6 alkyl optionally contains a heteroatom selected from the group consisting of —O—, —S—, —S(═O)—, —S(═O) 2 — and —NR 17 —.
18 . The compound of claim 16 , wherein said compound is of the Formula:
19 . The compound of claim 1 , according to Formula Ia
wherein:
R 1 is a member selected from the group consisting of C 6 -C 10 aryl substituted with 0-3 R 1a , 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 R 1a ;
each R 1a is independently a member selected from the group consisting of H, C 1 -C 3 perfluoroalkyl, C 3 -C 7 cycloalkyl, F, Cl, Br, CN, NO 2 , OR 10 , SCH 3 , S(═O)CH 3 , S(═O) 2 R 10 , NR 11 R 12 , acetyl, C(═O)OR 13 , C(═O)NR 13 R 14 , S(═O) 2 NR 13 R 14 , phenyl substituted with 0-3 R 15 ; and a C 1 -C 4 alkyl substituted with 0-2 R 16 ;
R 2 is a member selected from the group consisting of a phenyl substituted with 0-3 R 15 ; a 5- to 6-membered monocyclic 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 R 15 , a C 1 -C 6 alkyl, a C 1 -C 2 alkyl substituted with 1R 2a , a C 3 -C 7 cycloalkyl substituted with 0-2 R 19 ;
each R 2a is independently a member selected from the group consisting of a C 6 -C 10 aryl substituted with 0-3 R 15 ; 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 R 15 ; a C 3 -C 8 cycloalkyl substituted with 0-2 R 19 ; and a C 7 -C 11 bicycloalkyl substituted with 0-2 R 19 ; and
Ar is phenyl substituted with 0-3 R 29 , or alternatively, R 29 and R 9 are taken together to form a 5- to 7-membered fused heterocyclic ring containing 1-2 heteroatom(s) each independently a member selected from the group consisting of N, O and S; wherein said 5- to 7-membered fused heterocyclic ring is substituted with 0-2 R 19 .
20 . The compound of claim 19 , wherein said compound is of the Formula:
21 . The compound of claim 1 , wherein
R 5 and R 7 are taken together to form a C 5 -C 7 cycloalkyl substituted with 0-2 R 19 ; and Ar is phenyl substituted with 0-3 R 29 , or alternatively, R 29 and R 9 are taken together to form a 5- to 7-membered fused heterocyclic ring containing 1-2 heteroatom(s) each independently a member selected from the group consisting of N, O and S; wherein said 5- to 7-membered fused heterocyclic ring is substituted with 0-2 R 19 .
22 . The compound of claim 1 , according to Formula If
wherein:
Y is a member selected from the group consisting of a bond and —(CR 20 R 21 ) m —W—(CR 22 R 23 ) p —;
subscript p is the integer 1 or 2;
subscript m is 0 or 1;
W is a oxygen; and
Ar is phenyl substituted with 0-3 R 29 , or alternatively, R 29 and R 9 are taken together to form a 5- to 7-membered fused heterocyclic ring containing 1-2 heteroatom(s) each independently a member selected from the group consisting of N, O and S; wherein said 5- to 7-membered fused heterocyclic ring is substituted with 0-2 R 19 .
23 . The compound of claim 1 , according to Formula Ig:
wherein:
R 5 is a member selected from the group consisting of H, C 3 -C 7 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkyne, phenyl substituted with 0-2 R 15 ; 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 R 15 , a C 1 -C 6 alkyl substituted with 0-2 R 18 , wherein said C 1 -C 6 alkyl optionally contains a heteroatom selected from the group consisting of —O—, —S—, —S(═O)—, —S(═O) 2 — and —NR 17 —.
24 . The compound of claim 23 , according to Formula Ih:
25 . The compound of claim 1 , wherein
R 9 is H; and Ar is phenyl substituted with 0-3 R 29 , or alternatively, R 29 and R 9 are taken together to form a 5- to 7-membered fused heterocyclic ring containing 1-2 heteroatom(s) each independently a member selected from the group consisting of N, O and S; wherein said 5- to 7-membered fused heterocyclic ring is substituted with 0-2 R 19 .
26 . The compound of claim 1 , wherein said compound is a member selected from the compounds of Table I.
27 . A pharmaceutical composition comprising: a compound of Formula I:
or a pharmaceutically acceptable salt or prodrug thereof,
wherein:
R 1 is a member selected from the group consisting of H, C 6 -C 10 aryl substituted with 0-3 R 1a , 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 R 1a , a C 3 -C 8 cycloalkyl substituted with 0-2 R 1b , wherein said C 3 -C 8 cycloalkyl is saturated or unsaturated; and a C 3 -C 8 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 1c and is saturated or unsaturated;
each R 1a is independently a member selected from the group consisting of H, C 1 -C 3 perfluoroalkyl, C 3 -C 7 cycloalkyl, F, Cl, Br, CN, NO 2 , OR 10 , SCH 3 , S(═O)CH 3 , S(═O) 2 R 10 , NR 11 R 12 , acetyl, C(═O)OR 13 , C(═O)NR 13 R 14 , S(═O) 2 NR 13 R 14 , phenyl substituted with 0-3 R 15 , a 5- to 6-membered monocyclic 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 R 15 , a C 3 -C 8 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 1c and is saturated or unsaturated, and a C 1 -C 4 alkyl substituted with 0-2 R 16 ;
each R 1b is independently a member selected from the group consisting of H, OH, F, Cl, acetyl, ═O, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, CF 3 and OCF 3 ;
each R 1c is independently a member selected from the group consisting of H, OH, F, Cl, ═O, C 1 -C 6 alkyl substituted with 0-2 R 16 , C 1 -C 6 alkoxy, CF 3 , OCF 3 , C(═O)R 10 , S(═O) 2 R 10 , tBoc, Cbz; phenyl substituted with 0-3 R 15 ; a 5- to 6-membered monocyclic 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 R 15 ;
R 2 is a member selected from the group consisting of a phenyl substituted with 0-3 R 15 , a 5- to 6-membered monocyclic 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 R 15 , a C 1 -C 6 alkyl substituted with 0-2 R 2a , wherein said C 1 -C 6 alkyl optionally contains a heteroatom selected from the group consisting of —O—, —S—, and —S(═O) 2 —, a C 2 -C 6 alkenyl, a C 2 -C 6 alkynyl, a C 3 -C 7 cycloalkyl substituted with 0-2 R 19 , wherein said C 3 -C 7 cycloalkyl optionally contains a heteroatom selected from —O—, —S—, and —S(═O) 2 —, and a C 7 -C 11 bicycloalkyl substituted with 0-2 R 19 ;
each R 2a is independently a member selected from the group consisting of a C 6 -C 10 aryl substituted with 0-3 R 15 , 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 R 15 , a C 3 -C 8 cycloalkyl substituted with 0-2 R 19 , and a C 7 -C 11 bicycloalkyl substituted with 0-2 R 19 ;
R 3 is a member selected from the group consisting of H and C 1 -C 4 alkyl;
subscript n is 0 or 1;
R 4 is a member selected from the group consisting of H and C 1 -C 6 alkyl;
alternatively, R 2 and R 4 are taken together to form a C 5 -C 7 cycloalkyl substituted with 0-2 R 19 ;
R 5 is a member selected from the group consisting of H, C 3 -C 7 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkyne, phenyl substituted with 0-2 R 15 ; 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 R 15 , a C 1 -C 6 alkyl substituted with 0-2 R 18 , wherein said C 1 -C 6 alkyl optionally contains a heteroatom selected from the group consisting of —O—, —S—, —S(═O)—, —(S═O) 2 — and —NR 17 —;
Y is a member independently selected from the group consisting of a bond and —(CR 20 R 21 ) m —W—(CR 22 R 23 ) p —;
subscript p is 1 or 2;
subscript m is 0 or 1;
W is a member independently selected from the group consisting of a bond, —O—, —S—, —S(═O)—, —S(═O) 2 — and —NR 12 —;
X is selected from the group consisting of —C(═O)—, —OC(═O)—, —NR 24 C(═O)— and —S(═O) 2 —;
each of R 6 , R 7 , R 8 and R 9 is independently a member selected from the group consisting of H and C 1 -C 4 alkyl;
alternatively, R 5 and R 7 are taken together to form a C 5 -C 7 cycloalkyl substituted with 0-2 R 19 ;
alternatively, R 5 and R 9 are taken together to form a 6-7 membered heterocyclic ring containing 1-2 heteroatoms each independently a member selected from the group consisting of N, O and S;
Ar is a member selected from the group consisting of phenyl substituted with 0-3 R 29 , and 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 R 29 ;
each R 10 is independently a member selected from the group consisting of H, C 3 -C 7 cycloalkyl, a C 1 -C 3 perfluoroalkyl, a C 1 -C 4 alkyl substituted with 0-1 R 25 , a phenyl substituted with 0-3 R 15 ; 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 R 15 , and a C 3 -C 8 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 1c ;
each R 11 is independently a member selected from the group consisting of H, t BOC, Cbz, C 3 -C 8 cycloalkyl, (C 1 -C 6 alkyl)-C(═O)—, (C 1 -C 6 alkyl)-S(═O) 2 — and a C 1 -C 6 alkyl;
each of R 12 , R 13 and R 14 is independently a member selected from the group consisting of H and C 1 -C 4 alkyl;
alternatively, R 13 and R 14 on the same N atom are taken together to form a C 5 -C 7 heterocycle containing 1-2 heteroatoms each independently a member selected from the group consisting of N, O and S;
each R 15 is independently a member selected from the group consisting of H, OH, F, Cl, Br, I, CN, NO 2 , COOR 13 , C(═O)NR 13 R 14 , S(═O) 2 NR 13 R 14 , acetyl, —SCH 3 , —S(═O)CH 3 , —S(═O) 2 CH 3 , NR 26 R 27 , C 1 -C 6 alkoxy, C 1 -C 3 perfluoroalkyl, C 1 -C 3 perfluoroalkoxy and a C 1 -C 6 alkyl;
each R 16 is independently a member selected from the group consisting of H, OH, COOR 13 , C(═O)NR 13 R 14 , S(═O) 2 NR 13 R 14 , acetyl, —SCH 3 , —S(═O)CH 3 , —S(═O) 2 CH 3 , C 1 -C 6 alkoxy, NR 26 R 27 , a phenyl substituted with 0-3 R 15 , 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 R 15 , and a C 3 -C 8 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 15 and is saturated or unsaturated;
R 17 is a member selected from the group consisting of H and C 1 -C 4 alkyl;
each R 18 is independently a member selected from the group consisting of H, OH, F, Cl, CN, NO 2 , C(═O)OR 30 , C(═O)NR 13 R 14 , NR 11 R 12 , a C 1 -C 3 perfluoroalkyl, a C 1 -C 3 perfluoroalkoxy, a phenyl substituted with 0-3 R 15 , 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 R 15 , a C 3 -C 8 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 15 and is saturated or unsaturated; and C 3 -C 8 cycloalkyl;
each R 19 is a independently a member selected from the group consisting of C 1 -C 4 alkyl, F, Cl and C 1 -C 4 alkoxy, CF 3 and OCF 3 ;
alternatively, two R 19 on the same carbon may be combined to form C 3 -C 6 cycloalkyl;
each of R 20 , R 21 , R 22 and R 23 is independently a member selected from the group consisting of a bond, H, F, OH, C 1 -C 4 alkyl, and C 1 -C 3 alkylhydroxy;
alternatively, R 20 and R 21 or R 22 and R 23 are taken together to form a C 3 -C 6 cycloalkyl;
R 24 is a member selected from the group consisting of H and C 1 -C 4 alkyl;
each R 25 is independently a member selected from the group consisting of H, C 3 -C 7 cycloalkyl, a phenyl substituted with 0-3 R 15 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 0-2 R 15 ;
each R 26 is independently a member selected from the group consisting of H, C 1 -C 4 alkyl, (C 1 -C 4 alkyl)-C(═O)— and (C 1 -C 4 alkyl)-S(═O) 2 —;
each R 27 is independently a member selected from the group consisting of H and C 1 -C 4 alkyl;
alternatively, R 26 and R 27 on the same N atom are taken together to form a C 5 -C 7 heterocycle containing 1-2 heteroatoms each independently a member selected from the group consisting of N, O and S;
each R 28 is independently a member selected from the group consisting of H, a C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, a phenyl substituted with 0-3 R 15 , a benzyl substituted with 0-2 R 15 ;
each R 29 is independently a member selected from the group consisting of H, F, Cl, Br, I, CN, NO 2 , OR 28 , SR 28 , S(═O)R 28 , S(═O) 2 R 28 , S(═O) 2 NR 13 R 14 , NR 26 R 27 , acetyl, C(═O)NR 13 R 14 , C(═O)OR 13 , C 1 -C 6 alkyl, OCHF 2 , SCF 3 , OCF 3 , —C(═NH)NH 2 , and 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently a member selected from the group consisting of N, O and S;
alternatively, two R 29 substituted on adjacent atoms may be combined to form a 5 to 6 membered heterocyclic fused radical, wherein said 5 to 6 membered heterocyclic fused radical comprise 1 or 2 heteroatom(s) selected from O, S and N; wherein said 5 to 6 membered heterocyclic fused radical is substituted with 0-1 oxo;
alternatively, R 29 and R 9 are taken together to form a 5- to 7-membered fused heterocyclic ring containing 1-2 heteroatom(s) each independently a member selected from the group consisting of N, O and S; wherein said 5 to 7 membered fused heterocyclic ring is substituted with 0-2 R 19 ;
each R 30 is independently a member selected from the group consisting of H, C 3 -C 7 cycloalkyl, C 1 -C 4 alkyl substituted with 0-1 R 25 , a phenyl substituted with 0-3 R 15 , 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 R 15 ; with the proviso that R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are not all hydrogen; and
an excepient.
28 . The composition of claim 27 , wherein said compound is a member selected from the compounds of Table I.
29 . A method of selectively inhibiting cathepsin S activity in a mammal in need thereof, comprising administering to said mammal a therapeutically effective amount of a compound of Formula I:
or a pharmaceutically acceptable salt or prodrug thereof,
wherein:
R 1 is a member selected from the group consisting of H, C 6 -C 10 aryl substituted with 0-3 R 1a , 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 R 1a , a C 3 -C 8 cycloalkyl substituted with 0-2 R 1b , wherein said C 3 -C 8 cycloalkyl is saturated or unsaturated; and a C 3 -C 8 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 1c and is saturated or unsaturated;
each R 1a is independently a member selected from the group consisting of H, C 1 -C 3 perfluoroalkyl, C 3 -C 7 cycloalkyl, F, Cl, Br, CN, NO 2 , OR 10 , SCH 3 , S(═O)CH 3 , S(═O) 2 R 10 , NR 11 R 12 , acetyl, C(═O)OR 13 , C(═O)NR 13 R 14 , S(═O) 2 NR 13 R 14 , phenyl substituted with 0-3 R 15 , a 5- to 6-membered monocyclic 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 R 15 , a C 3 -C 8 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 1c and is saturated or unsaturated, and a C 1 -C 4 alkyl substituted with 0-2 R 16 ;
each R 1b is independently a member selected from the group consisting of H, OH, F, Cl, acetyl, ═O, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, CF 3 and OCF 3 ;
each R 1c is independently a member selected from the group consisting of H, OH, F, Cl, ═O, C 1 -C 6 alkyl substituted with 0-2 R 16 , C 1 -C 6 alkoxy, CF 3 , OCF 3 , C(═O)R 10 , S(═O) 2 R 10 , tBoc, Cbz; phenyl substituted with 0-3 R 15 ; a 5- to 6-membered monocyclic 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 R 15 ;
R 2 is a member selected from the group consisting of a phenyl substituted with 0-3 R 15 , a 5- to 6-membered monocyclic 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 R 15 , a C 1 -C 6 alkyl substituted with 0-2 R 2a , wherein said C 1 -C 6 alkyl optionally contains a heteroatom selected from the group consisting of —O—, —S—, and —S(═O) 2 —, a C 2 -C 6 alkenyl, a C 2 -C 6 alkynyl, a C 3 -C 7 cycloalkyl substituted with 0-2 R 19 , wherein said C 3 -C 7 cycloalkyl optionally contains a heteroatom selected from —O—, —S—, and —S(═O) 2 —, and a C 7 -C 11 bicycloalkyl substituted with 0-2 R 19 ;
each R 2a is independently a member selected from the group consisting of a C 6 -C 10 aryl substituted with 0-3 R 15 , 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 R 15 , a C 3 -C 8 cycloalkyl substituted with 0-2 R 19 , and a C 7 -C 11 bicycloalkyl substituted with 0-2 R 19 ;
R 3 is a member selected from the group consisting of H and C 1 -C 4 alkyl;
subscript n is 0 or 1;
R 4 is a member selected from the group consisting of H and C 1 -C 6 alkyl;
alternatively, R 2 and R 4 are taken together to form a C 5 -C 7 cycloalkyl substituted with 0-2 R 19 ;
R 5 is a member selected from the group consisting of H, C 3 -C 7 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkyne, phenyl substituted with 0-2 R 15 ; 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 R 15 , a C 1 -C 6 alkyl substituted with 0-2 R 18 , wherein said C 1 -C 6 alkyl optionally contains a heteroatom selected from the group consisting of —O—, —S—, —S(═O)—, —S(═O) 2 — and —NR 17 —;
Y is a member independently selected from the group consisting of a bond and —(CR 20 R 21 ) m —W—(CR 22 R 23 ) p —;
subscript p is 1 or 2;
subscript m is 0 or 1;
W is a member independently selected from the group consisting of a bond, —O—, —S—, —S(═O)—, —S(═O) 2 — and —NR 12 —;
X is selected from the group consisting of —C(═O)—, —OC(═O)—, —NR 24 C(═O)— and —S(═O) 2 —;
each of R 6 , R 7 , R 8 and R 9 is independently a member selected from the group consisting of H and C 1 -C 4 alkyl;
alternatively, R 5 and R 7 are taken together to form a C 5 -C 7 cycloalkyl substituted with 0-2 R 19 ;
alternatively, R 5 and R 9 are taken together to form a 6-7 membered heterocyclic ring containing 1-2 heteroatoms each independently a member selected from the group consisting of N, O and S;
Ar is a member selected from the group consisting of phenyl substituted with 0-3 R 29 , and 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 R 29 ;
each R 10 is independently a member selected from the group consisting of H, C 3 -C 7 cycloalkyl, a C 1 -C 3 perfluoroalkyl, a C 1 -C 4 alkyl substituted with 0-1 R 25 , a phenyl substituted with 0-3 R 15 ; 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 R 15 , and a C 3 -C 8 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 1c ;
each R 11 is independently a member selected from the group consisting of H, t BOC, Cbz, C 3 -C 8 cycloalkyl, (C 1 -C 6 alkyl)-C(═O)—, (C 1 -C 6 alkyl)-S(═O) 2 — and a C 1 -C 6 alkyl;
each of R 12 , R 13 and R 14 is independently a member selected from the group consisting of H and C 1 -C 4 alkyl;
alternatively, R 13 and R 14 on the same N atom are taken together to form a C 5 -C 7 heterocycle containing 1-2 heteroatoms each independently a member selected from the group consisting of N, O and S;
each R 15 is independently a member selected from the group consisting of H, OH, F, Cl, Br, I, CN, NO 2 , COOR 13 , C(═O)NR 13 R 14 , S(═O) 2 NR 13 R 14 , acetyl, —SCH 3 , —S(═O)CH 3 , —S(═O) 2 CH 3 , NR 26 R 27 , C 1 -C 6 alkoxy, C 1 -C 3 perfluoroalkyl, C 1 -C 3 perfluoroalkoxy and a C 1 -C 6 alkyl;
each R 16 is independently a member selected from the group consisting of H, OH, COOR 13 , C(═O)NR 13 R 14 , S(═O) 2 NR 13 R 14 , acetyl, —SCH 3 , —S(═O)CH 3 , —S(═O) 2 CH 3 , C 1 -C 6 alkoxy, NR 26 R 27 , a phenyl substituted with 0-3 R 15 , 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 R 15 , and a C 3 -C 8 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 15 and is saturated or unsaturated;
R 17 is a member selected from the group consisting of H and C 1 -C 4 alkyl;
each R 18 is independently a member selected from the group consisting of H, OH, F, Cl, CN, NO 2 , C(═O)OR 30 , C(═O)NR 13 R 14 , NR 11 R 12 , a C 1 -C 3 perfluoroalkyl, a C 1 -C 3 perfluoroalkoxy, a phenyl substituted with 0-3 R 15 , 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 R 15 , a C 3 -C 8 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 15 and is saturated or unsaturated; and C 3 -C 8 cycloalkyl;
each R 19 is a independently a member selected from the group consisting of C 1 -C 4 alkyl, F, Cl and C 1 -C 4 alkoxy, CF 3 and OCF 3 ;
alternatively, two R 19 on the same carbon may be combined to form C 3 -C 6 cycloalkyl;
each of R 20 , R 21 , R 22 and R 23 is independently a member selected from the group consisting of a bond, H, F, OH, C 1 -C 4 alkyl, and C 1 -C 3 alkylhydroxy;
alternatively, R 20 and R 21 or R 22 and R 23 are taken together to form a C 3 -C 6 cycloalkyl;
R 24 is a member selected from the group consisting of H and C 1 -C 4 alkyl;
each R 25 is independently a member selected from the group consisting of H, C 3 -C 7 cycloalkyl, a phenyl substituted with 0-3 R 15 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 0-2 R 15 ;
each R 26 is independently a member selected from the group consisting of H, C 1 -C 4 alkyl, (C 1 -C 4 alkyl)-C(═O)— and (C 1 -C 4 alkyl)-S(═O) 2 —;
each R 27 is independently a member selected from the group consisting of H and C 1 -C 4 alkyl;
alternatively, R 26 and R 27 on the same N atom are taken together to form a C 5 -C 7 heterocycle containing 1-2 heteroatoms each independently a member selected from the group consisting of N, O and S;
each R 28 is independently a member selected from the group consisting of H, a C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, a phenyl substituted with 0-3 R 15 , a benzyl substituted with 0-2 R 15 ;
each R 29 is independently a member selected from the group consisting of H, F, Cl, Br, I, CN, NO 2 , OR 28 , SR 28 , S(═O)R 28 , S(═O) 2 R 28 , S(═O) 2 NR 13 R 14 , NR 26 R 27 , acetyl, C(═O)NR 13 R 14 , C(═O)OR 13 , C 1 -C 6 alkyl, OCHF 2 , SCF 3 , OCF 3 , —C(═NH)NH 2 , and 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently a member selected from the group consisting of N, O and S;
alternatively, two R 29 substituted on adjacent atoms may be combined to form a 5 to 6 membered heterocyclic fused radical, wherein said 5 to 6 membered heterocyclic fused radical comprise 1 or 2 heteroatom(s) selected from O, S and N; wherein said 5 to 6 membered heterocyclic fused radical is substituted with 0-1 oxo;
alternatively, R 29 and R 9 are taken together to form a 5- to 7-membered fused heterocyclic ring containing 1-2 heteroatom(s) each independently a member selected from the group consisting of N, O and S; wherein said 5 to 7 membered fused heterocyclic ring is substituted with 0-2 R 19 ;
each R 30 is independently a member selected from the group consisting of H, C 3 -C 7 cycloalkyl, C 1 -C 4 alkyl substituted with 0-1 R 25 , a phenyl substituted with 0-3 R 15 , 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 R 15 ; and
with the proviso that R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are not all hydrogen.
30 . The method of claim 29 , wherein the cathepsin S inhibition constant for a compound of Formula I is less than 10 μM.
31 . The method of claim 30 , wherein the cathepsin S inhibition constant for a compound of Formula I is less than 1.0 μM.
32 . The method of claim 31 , wherein the cathepsin S inhibition constant for a compound of Formula I is less than 0.1 μM.
33 . The method of claim 29 , wherein cathepsin S is selectively inhibited in the presence of at least one other cathepsin.
34 . The method of claim 33 , wherein the inhibition constant of a compound of Formula I for said at least one other cathepsin is at least 10 times greater than a cathepsin S inhibition constant of a compound of Formula I.
35 . The method of claim 34 , wherein the inhibition constant of a compound of Formula I for said at least one other cathepsin is at least 100 times greater than said cathepsin S inhibition constant of a compound of Formula I.
36 . The method of claim 35 , wherein the inhibition constant of a compound of Formula I for said at least one other cathepsin is at least 1000 times greater than said cathepsin S inhibition constant of a compound of Formula I.
37 . The method of claim 29 , wherein said compound is a member selected from the compounds of Table I.
38 . The compound of claim 1 , selected from the group consisting of:
N-{cis-2-[2-(4-Methoxy-phenylamino)-ethylcarbamoyl]-cyclohexyl}-3-methyl-benzamide; 5-(3-Trifluoromethyl-phenyl)-furan-2-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; 1-Benzoyl-piperidine-4-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; Furan-2-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; Furan-3-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; 1-(4-Chloro-benzenesulfonyl)-piperidine-4-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; N-{1-(S)-[2-(4-Methoxy-phenylamino)-propylcarbamoyl]-3-methyl-butyl}-3-methyl-benzamide; N-{1-(S)-[2-(4-Methoxy-phenylamino)-1-methyl-ethylcarbamoyl]-3-methyl-butyl}-3-methyl-benzamide; N-{1-(S)-[2-(4-Methoxy-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-3-methyl-butyl}-3-methyl-benzamide; N-{1-(S)-[2-(4-Methoxy-phenylamino)-1-(R)-methyl-ethylcarbamoyl]-3-methyl-butyl}-3-methyl-benzamide; 1H-Indole-2-carboxylic acid {3-cyclohexyl-(1S)-[2-(4-methoxy-phenylamino)-(1S)-methyl-ethylcarbamoyl]-propyl}-amide; 1H-Indole-2-carboxylic acid {3-cyclohexyl-(1S)-[2-(4-methoxy-phenylamino)-(1R)-methyl-ethylcarbamoyl]-propyl}-amide; N-{2-Cyclohexyl-(1S)-[2-(4-methoxy-phenylamino)-(1R)-methyl-ethylcarbamoyl]-ethyl}-3-methoxy-benzamide; 5-(3-Trifluoromethyl-phenyl)-furan-2-carboxylic acid {3-cyclohexyl-(1S)-[2-(4-methoxy-phenylamino)-(1S)-methyl-ethylcarbamoyl]-propyl}-amide; Tetrahydrofuran-2-(S)-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-amide; Tetrahydrofuran-2-(R)-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-amide; N-{1-(S)-[1-(4-Methoxy-phenyl)-piperidin-3-(S)-ylcarbamoyl]-3-methyl-butyl}-3-methyl-benzamide; N-{1-(S)-[1-(4-Methoxy-phenyl)-piperidin-3-(R)-ylcarbamoyl]-3-methyl-butyl}-3-methyl-benzamide; N-{1-(S)-[cis-2-(4-Methoxy-phenylamino)-cyclohexylcarbamoyl]-3-methyl-butyl}-3-methyl-benzamide; N-{1-(S)-[trans-2-(4-Methoxy-phenylamino)-cyclohexylcarbamoyl]-3-methyl-butyl}-3-methyl-benzamide; N-{1-(S)-[1-(R)-Benzyloxymethyl-2-(4-methoxy-phenylamino)-ethylcarbamoyl]-3-methyl-butyl}-3-methyl-benzamide; N—(S)-{[1-(R)-Benzyloxymethyl-2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-phenyl-methyl}-3-methoxy-benzamide; N-[1-(S)-[1-(R)-Benzyloxymethyl-2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-2-(4-fluoro-phenyl)-ethyl]-3-methoxy-benzamide; N-{1-(S)-[(2-Benzyloxy-1-(R)-(5-fluoro-2,3-dihydro-indol-1-ylmethyl)-ethylcarbamoyl]-3-cyclohexyl-propyl}-3-methoxy-benzamide; 1H-Indole-2-carboxylic acid {(1S)-[2-benzyloxy-(1R)-(5-fluoro-2,3-dihydro-indol-1-ylmethyl)-ethylcarbamoyl]-3-cyclohexyl-propyl}-amide; (S,S)—N-{1-[1-(5-Fluoro-2,3-dihydro-indol-1-ylmethyl)-3-ureido-propylcarbamoyl]-3-methyl-butyl}-3-methyl-benzamide; (S,S)—N-{3-Cyclohexyl-1-[1-(5-fluoro-2,3-dihydro-indol-1-ylmethyl)-3-morpholin-4-yl-propylcarbamoyl]-propyl}-3-methoxy-benzamide; N-{1-(S)-[2-(R)-Benzyloxy-1-(R)-(5-fluoro-2,3-dihydro-indol-1-ylmethyl)-propylcarbamoyl]-3-cyclohexyl-propyl}-3-methoxy-benzamide; N-{1-(R)-[1-(R)-Benzylsulfanylmethyl-2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-3-cyclohexyl-propyl}-3-methoxy-benzamide; (S,S)-[5-[4-Cyclohexyl-2-(3-methoxy-benzoylamino)-butyrylamino]-6-(5-fluoro-2,3-dihydro-indol-1-yl)-hexyl]-carbamic acid benzyl ester; 1-(6-Chloro-pyridazin-3-yl)-piperidine-4-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; 1-(4-Methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; 1-Benzenesulfonyl-piperidine-4-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; 1-Methyl-1H-imidazole-4-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; 1-Benzyl-5-oxo-pyrrolidine-3-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; 1-(4-Fluoro-benzenesulfonyl)-piperidine-4-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; N—(S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-4-(piperidin-4-yloxy)-benzamide; N—(S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-4-(1-methanesulfonyl-piperidin-4-yloxy)-benzamide; 4-(1-Acetyl-piperidin-4-yloxy)-N—(S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-benzamide; 5-Methanesulfonyl-thiophene-2-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; 5-Oxo-1-thiophen-2-ylmethyl-pyrrolidine-3-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; 1-Furan-2-ylmethyl-5-oxo-pyrrolidine-3-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; 5-Phenyl-furan-2-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; 2-Phenyl-thiazole-4-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; 1-Methanesulfonyl-piperidine-4-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]ethyl}-amide; 5-Methyl-2-trifluoromethyl-furan-3-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-amide; 5-Phenyl-thiophene-2-carboxylic acid (S)-{2-cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(4-difluoromethoxy-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(benzo[1,3]dioxol-5-ylamino)-1-(S)-methyl-ethylcarbamoyl]-2-cyclohexyl-ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(4-methoxy-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(3,5-difluoro-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(3-methanesulfonyl-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(4-methanesulfonyl-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(2,3-difluoro-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(2,5-difluoro-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(2,6-difluoro-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(4-cyano-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-2-cyclohexyl-ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(3-chloro-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-2-cyclohexyl-ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(2-fluoro-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(3-chloro-2-fluoro-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-2-cyclohexyl-ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(5-chloro-2-fluoro-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-2-cyclohexyl-ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(3-carbamoyl-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-2-cyclohexyl-ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(3-fluoro-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(3-cyano-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-2-cyclohexyl-ethyl}-amide; 5-(4-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]ethyl}-amide; 5-(4-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(4-difluoromethoxy-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(4-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(4-methoxy-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(4-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(3-methanesulfonyl-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(4-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(4-methanesulfonyl-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 3-(3-Fluoro-phenyl)-[1,2,4]oxadiazole-5-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-amide; 3-(4-Fluoro-phenyl)-[1,2,4]oxadiazole-5-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-amide; 3-[2-(S)-(3-Cyclohexyl-2-(S)- {[5-(3-fluoro-phenyl)-furan-2-carbonyl]-amino}-propionylamino)-propylamino]-benzoic acid methyl ester; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(3-trifluoromethoxy-phenylamino)-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(2-chloro-5-fluoro-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-2-cyclohexyl-ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(2-chloro-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-2-cyclohexyl-ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(4-methoxy-2,6-dimethyl-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(4-methoxy-3,5-dimethyl-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(2-methanesulfonyl-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-methylsulfanyl-phenylamino)-ethylcarbamoyl]-ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-methylsulfamoyl-phenylamino)-ethylcarbamoyl]-ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethylsulfanyl-phenylamino)-ethylcarbamoyl]-ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(3-dimethylcarbamoyl-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(2-carbamoyl-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-2-cyclohexyl-ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(4-dimethylcarbamoyl-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 3-Cyclohexyl-2-(S)-(3-methoxy-propionylamino)-N-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethyl]-propionamide; 3-Cyclohexyl-2-(S)-(2-methoxy-acetylamino)-N-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethyl]-propionamide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(4-hydroxy-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(4-fluoro-phenylamino)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {3,3-dimethyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-butyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(4-difluoromethoxy-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-3,3-dimethyl-butyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(4-methanesulfonyl-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-3,3-dimethyl-butyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(3-methanesulfonyl-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-3,3-dimethyl-butyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(3-carbamoyl-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-3,3-dimethyl-butyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(4-methoxy-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-3,3-dimethyl-butyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(5-methyl-isoxazol-3-ylamino)-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(3-acetylamino-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-2-cyclohexyl-ethyl}-amide; Tetrahydropyran-4-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid (2-cyclohexyl-1-(S)-{1-(S)-methyl-2-[4-(morpholine-4-sulfonyl)-phenylamino]-ethylcarbamoyl}-ethyl)-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(3-oxo-1,3-dihydro-isobenzofuran-5-ylamino)-ethylcarbamoyl]ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-sulfamoyl-phenylamino)-ethylcarbamoyl]-ethyl}-amide; Tetrahydropyran-4-carboxylic acid {2-cyclohexyl-1-(S)-[2-(5-fluoro-2,2-dimethyl-2,3-dihydro-indol-1-yl)-1-(S)-methyl-ethylcarbamoyl]-ethyl}-amide; Tetrahydrofuran-3-carboxylic acid {2-cyclohexyl-1-(S)-[2-(5-fluoro-2,2-dimethyl-2,3-dihydro-indol-1-yl)-1-(S)-methyl-ethylcarbamoyl]-ethyl}-amide; 1-(3-Fluoro-phenyl)-1H-pyrazole-4-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]ethyl}-amide; 1-(4-Fluoro-phenyl)-1H-pyrazole-4-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]ethyl}-amide; 5-Pyridin-3-yl-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-amide; 5-(1-Oxy-pyridin-3-yl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-amide; 3-(3-Fluoro-phenyl)-isoxazole-5-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-amide; 3-(4-Fluoro-phenyl)-isoxazole-5-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-amide; 5-(3-Fluoro-phenyl)-[1,3,4]oxadiazole-2-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-amide; N-{1-(S)-[1-(R)-Benzyloxymethyl-2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-2-cyclohexyl-ethyl}-3-methoxy-benzamide; N-{2-Cyclohexyl-1-(S)-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-1-(S)-morpholin-4-ylmethyl-ethylcarbamoyl]-ethyl}-3-methoxy-benzamide; 5-(3-Trifluoromethyl-phenyl)-furan-2-carboxylic acid {1-(S)-[1-(R)-benzyloxymethyl-2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-2-cyclohexyl-ethyl}-amide; 5-(3-Trifluoromethyl-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-1-(R)-hydroxymethyl-ethylcarbamoyl]ethyl}-amide; {1-(S)-[1-(R)-Benzyloxymethyl-2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-3,3-dimethyl-butyl}-carbamic acid tert-butyl ester; N-{1-(S)-[1-(R)-Benzyloxymethyl-2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-3,3-dimethyl-butyl}-3-methoxy-benzamide {1-(S)-[1-(S)-(5-Fluoro-2,3-dihydro-indol-1-ylmethyl)-3-methanesulfonyl-propylcarbamoyl]-3,3-dimethyl-butyl}-carbamic acid tert-butyl ester; 3-(S)-(2-(S)-Benzyloxycarbonylamino-4,4-dimethyl-pentanoylamino)-4-(5-fluoro-2,3-dihydro-indol-1-yl)-butyric acid tert-butyl ester; 3-(S)-(2-(S)-Benzyloxycarbonylamino-4,4-dimethyl-pentanoylamino)-4-(5-fluoro-2,3-dihydro-indol-1-yl)-butyric acid; {1-(S)-[2-Cyano-1-(S)-(5-fluoro-2,3-dihydro-indol-1-ylmethyl)-ethylcarbamoyl]-3,3-dimethyl-butyl}-carbamic acid tert-butyl ester; N-{1-(S)-[2-(5-Fluoro-2,3-dihydro-indol-1-yl)-1-(S)-(1H-tetrazol-5-ylmethyl)-ethylcarbamoyl]-3,3-dimethyl-butyl}-3-methoxy-benzamide; 3-(S)-(2-(S)-Benzyloxycarbonylamino-3-cyclohexyl-propionylamino)-4-(5-fluoro-2,3-dihydro-indol-1-yl)-butyric acid benzyl ester; 1-(S)-[1-(R)-Benzyloxymethyl-2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-2-cyclohexyl-ethyl}-carbamic acid benzyl ester; N-{3-Cyclohexyl-1-(S)-[2-(3,5-dimethoxy-benzyloxy)-1-(R)-(5-fluoro-2,3-dihydro-indol-1-ylmethyl)-ethylcarbamoyl]-propyl}-3-methoxy-benzamide; 4-{2-(R)-[4-Cyclohexyl-2-(S)-(3-methoxy-benzoylamino)-butyrylamino]-3-(5-fluoro-2,3-dihydro-indol-1-yl)-propoxymethyl}-benzoic acid methyl ester; Tetrahydropyran-4-carboxylic acid {2-cyclohexyl-1-(S)-[2-(5-fluoro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-1-(S)-methyl-ethylcarbamoyl]-ethyl}-amide; {2-Cyclohexyl-1-(S)-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-1-(S)-methyl-ethylcarbamoyl]-ethyl}-carbamic acid benzyl ester; 4-Benzyloxy-N—(R,S)-{[2-(4-amidinophenylamino)-1-(S)-methyl-ethylcarbamoyl]-(2,4-dichloro-phenyl)-methyl}-benzamide; {1-(S)-[2-(5-Fluoro-2,3-dihydro-indol-1-yl)-1-(S)-methyl-ethylcarbamoyl]-3,3-dimethyl-butyl}-carbamic acid benzyl ester; Pyridazine-4-carboxylic acid {1-(S)-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-1-(S)-methyl-ethylcarbamoyl]-3,3-dimethyl-butyl}-amide; 4,4-Dimethyl-2-(S)-(2-1H-tetrazol-5-yl-acetylamino)-pentanoic acid [2-(5-fluoro-2,3-dihydro-indol-1-yl)-1-(S)-methyl-ethyl]-amide; (2-Cyclohexyl-1-(S)-{1-(S)-methyl-2-[3-(1H-tetrazol-5-yl)-phenylamino]-ethylcarbamoyl}-ethyl)-carbamic acid benzyl ester; (S,S)-2-(3-Chloro-benzenesulfonylamino)-3-cyclohexyl-N-[1-methyl-2-(4-trifluoromethoxy-phenylamino)-ethyl]-propionamide; (S,S)-3-Cyclohexyl-N-[1-methyl-2-(4-trifluoromethoxy-phenylamino)-ethyl]-2-(3-trifluoromethoxy-benzenesulfonylamino)-propionamide; (S,S)-3-Cyclohexyl-N-[1-methyl-2-(4-trifluoromethoxy-phenylamino)-ethyl]-2-(pyridine-3-sulfonylamino)-propionamide; (S,S)-{2-Cyclohexyl-1-[1-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-carbamic acid tetrahydro-pyran-4-yl ester; 3-(R)-{2-Cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethylcarbamoyloxy}-pyrrolidine-1-carboxylic acid tert-butyl ester; (S,S)-{2-Cyclohexyl-1-[1-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-carbamic acid 1,1-dioxo-hexahydro-1λ 6 -thiopyran-4-yl ester; {2-Cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-carbamic acid pyrrolidin-3-(R)-yl ester; {2-Cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-carbamic acid tetrahydrofuran-3-(R)-yl ester; {2-Cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-carbamic acid tetrahydrofuran-3-(S)-yl ester; (S,S)-{2-Cyclopentyl-1-[1-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-carbamic acid tetrahydropyran-4-yl ester; (S,S)-{2-Cyclopentyl-1-[1-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-carbamic acid tetrahydrofuran-3-(R)-yl ester; (S,S)-{2-Cyclopentyl-1-[1-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-carbamic acid tetrahydrofuran-3-(S)-yl ester; N—((S)-1-(2-(5-fluoroindolin-1-yl)ethylcarbamoyl)-2-cyclopropylethyl)-5-(3-(trifluoromethyl)phenyl)furan-2-carboxamide; N—((S)-1-(2-(5-fluoroindolin-1-yl)ethylcarbamoyl)-2-(3-chlorophenyl)ethyl)-5-(3-(trifluoromethyl)phenyl)furan-2-carboxamide; N—((S)-1-(2-(5-fluoroindolin-1-yl)ethylcarbamoyl)-2-(4-chlorophenyl)ethyl)-5-(3-(trifluoromethyl)phenyl)furan-2-carboxamide; N—((S)-1-(2-(5-fluoroindolin-1-yl)ethylcarbamoyl)-2-cyclopentylethyl)-5-(3-(trifluoromethyl)phenyl)furan-2-carboxamide; N—((S)-1-(2-(5-fluoroindolin-1-yl)ethylcarbamoyl)-3,3-dimethylbutyl)-5-(3-(trifluoromethyl)phenyl)furan-2-carboxamide; N—((S)-1-(2-(5-fluoroindolin-1-yl)ethylcarbamoyl)-2-phenylethyl)-5-(3-(trifluoromethyl)phenyl)furan-2-carboxamide; N—(R,S)-((3-(benzyloxy)-1-(5-fluoroindolin-1-yl)propan-2-(R)-ylcarbamoyl)(2,4-dichlorophenyl)methyl)furan-2-carboxamide; N—(S)-((3-(5-fluoroindolin-1-yl)-1-hydroxypropan-2-(R)-ylcarbamoyl)(2,4-dichlorophenyl)methyl)furan-2-carboxamide; (S,S)-3-Cyclohexyl-2-(2,4-dimethyl-thiazole-5-sulfonylamino)-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-1-methyl-ethyl]-propionamide; N—(S)-((3-(benzyloxy)-1-(5-fluoroindolin-1-yl)propan-2-(R)-ylcarbamoyl)(2,4-dichlorophenyl)methyl)-3,4-difluorobenzamide; N—-(S)-((3-(5-fluoroindolin-1-yl)-1-hydroxypropan-2-(R)-ylcarbamoyl)(2,4-dichlorophenyl)methyl)furan-2-carboxamide; (S,S)-{2-Cyclohexyl-1-[2-(5-fluoro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-1-methyl-ethylcarbamoyl]-ethyl}-carbamic acid tetrahydro-pyran-4-yl ester; {2-Cyclohexyl-1-(S)-[2-(5-fluoro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-1-(S)-methyl-ethylcarbamoyl]-ethyl}-carbamic acid (R)-tetrahydrofuran-3-yl ester; (S,S)-{2-Cyclohexyl-1-[2-(5-fluoro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-1-methyl-ethylcarbamoyl]-ethyl}-carbamic acid (S)-tetrahydro-furan-3-yl ester; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-[3-(5-phenyl-thiophen-2-yl)-ureido]-propionamide; (S)-3-Cyclohexyl-2-[3-(3,5-dimethyl-isoxazol-4-yl)-ureido]-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-(5-methyl-1-phenyl-1H-pyrazole-4-sulfonylamino)-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-(5-isoxazol-3-yl-thiophene-2-sulfonylamino)-propionamide; (S)-{2-Cyclohexyl-1-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethylcarbamoyl]-ethyl}-carbamic acid benzyl ester; (S)-2-(4-Bromo-3-chloro-thiophene-2-sulfonylamino)-3-cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-propionamide; (S)-2-(3-Biphenyl-4-yl-ureido)-3-cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-(4-phenoxy-benzenesulfonylamino)-propionamide; (S)-2-(5-Chloro-thiophene-2-sulfonylamino)-3-cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-(naphthalene-1-sulfonylamino)-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-(4-trifluoromethyl-benzenesulfonylamino)-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-(4-trifluoromethoxy-benzenesulfonylamino)-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-[5-(2-methyl-5-trifluoromethyl-2H-pyrazol-3-yl)-thiophene-2-sulfonylamino]-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-(3-methyl-3H-imidazole-4-sulfonylamino)-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-[3-(5-methyl-[1,3,4]oxadiazol-2-yl)-benzenesulfonylamino]-propionamide; (S)-2-(Benzo[b]thiophene-2-sulfonylamino)-3-cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-(thiophene-2-sulfonylamino)-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-[4-(4-fluoro-phenoxy)-benzenesulfonylamino]-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-[5-(2-methyl-thiazol-4-yl)-thiophene-2-sulfonylamino]-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-(4′-methoxy-biphenyl-4-sulfonylamino)-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-(4-methoxy-benzenesulfonylamino)-propionamide; (S)-3-Cyclohexyl-2-(4-difluoromethoxy-benzenesulfonylamino)-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-propionamide; (S)-2-(5-Chloro-1,3-dimethyl-1H-pyrazole-4-sulfonylamino)-3-cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-phenylmethanesulfonylamino-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-(toluene-3-sulfonylamino)-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-[4-(4-methoxy-phenoxy)-benzenesulfonylamino]-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-(3-methoxy-benzenesulfonylamino)-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-(4-oxazol-5-yl-benzenesulfonylamino)-propionamide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(3-methyl-isoxazol-5-ylamino)-ethylcarbamoyl]ethyl}-amide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-(thiophene-3-sulfonylamino)-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-methanesulfonylamino-propionamide; (S,S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-1-methyl-ethyl]-2-(5-oxazol-5-yl-thiophene-3-sulfonylamino)-propionamide; (S,S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-1-methyl-ethyl]-2-(toluene-3-sulfonylamino)-propionamide; (S,S)-3-[4,4-Dimethyl-2-(toluene-3-sulfonylamino)-pentanoylamino]-4-(5-fluoro-2,3-dihydro-indol-1-yl)-butyric acid tert-butyl ester; (S,S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-1-methyl-ethyl]-2-(2-methyl-4-trifluoromethyl-furan-3-sulfonylamino)-propionamide; (S,S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-1-methyl-ethyl]-2-(3-trifluoromethoxy-benzenesulfonylamino)-propionamide; (S)-3-Cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-2-(1-methyl-1H-imidazole-4-sulfonylamino)-propionamide; (S)-2-(5-Benzenesulfonyl-thiophene-2-sulfonylamino)-3-cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-propionamide; (S)-2-(2-Acetylamino-4-methyl-thiazole-5-sulfonylamino)-3-cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-propionamide; (S)-3-Cyclohexyl-2-(4,5-dichloro-thiophene-2-sulfonylamino)-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-ethyl]-propionamide; (S,S)-2-(3-Chloro-benzenesulfonylamino)-3-cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-1-methyl-ethyl]-propionamide; (S,S)-3-(2-tert-Butoxycarbonylamino-3-cyclohexyl-propionylamino)-4-(5-fluoro-2,3-dihydro-indol-1-yl)-butyric acid benzyl ester; (S,S)-3-[4,4-Dimethyl-2-(toluene-3-sulfonylamino)-pentanoylamino]-4-(5-fluoro-2,3-dihydro-indol-1-yl)-butyric acid; (S,S)-3-Cyclohexyl-2-(3,5-dimethyl-isoxazole-4-sulfonylamino)-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-1-methyl-ethyl]-propionamide; (S,S)-2-Benzenesulfonylamino-3-cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-indol-1-yl)-1-methyl-ethyl]-propionamide; (S,S)-4,4-Dimethyl-2-(toluene-3-sulfonylamino)-pentanoic acid [2-(5-fluoro-2,3-dihydro-indol-1-yl)-1-methyl-ethyl]-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {1-(S)-[2-(4-benzyloxy-phenylamino)-1-(S)-methyl-ethylcarbamoyl]-2-cyclohexyl-ethyl}-amide; 5-(3-Fluoro-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(3-methyl-isothiazol-5-ylamino)-ethylcarbamoyl]ethyl}-amide; Tetrahydrofuran-2-(R)-carboxylic acid {3,3-dimethyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-butyl}-amide; Tetrahydropyran-4-carboxylic acid {3,3-dimethyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-butyl}-amide; Tetrahydro-pyran-4-carboxylic acid {1-(S)-[2-(5-fluoro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-1-(S)-methyl-ethylcarbamoyl]-3,3-dimethyl-butyl}-amide; Tetrahydro-furan-2-(R)-carboxylic acid {1-(S)-[2-(5-fluoro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-1-(S)-methyl-ethylcarbamoyl]-3,3-dimethyl-butyl}-amide; Tetrahydrofuran-3-(R,S)-carboxylic acid {2-cyclohexyl-1-(S)-[1-(S)-methyl-2-(4-trifluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-amide; Tetrahydrofuran-2-(R)-carboxylic acid {2-cyclohexyl-1-(S)-[2-(5-fluoro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide, and Tetrahydrofuran-2-(R)-carboxylic acid {2-cyclohexyl-1-(S)-[2-(5-fluoro-2,2-dimethyl-2,3-dihydro-indol-1-yl)-1-(S)-methyl-ethylcarbamoyl]ethyl}-amide.Cited by (0)
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