Substituted benzimidazoles as nociceptin receptor modulators

1. A compound of formula (I)

wherein

X is (CHR) n wherein n=1, 2, or 3; or X is absent;

R 1 is halo, nitro, cyano, (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)alkylsulfonyl, (C1-C6)alkoxy, trifluoromethoxy, or (C1-C6)haloalkylsulfonyl, and m=0, 1, or 2;

R 2 and R 3 are independently H, (C1-C6)alkyl, (C1-C6)alkyl substituted with 1-5 fluorine atoms, or (C1-C6)cycloalkyl;

R 4 is (C1-C10)alkyl, (C3-C10) mono- or bicyclic cycloalkyl, (C3-C10) mono- or bicyclic cycloalkenyl, (C3-C10) mono- or bicyclic cycloalkyl(C1-C6)alkyl, (C3-C10) mono- or bicyclic cycloalkyl(C1-C6)alkenyl, or 3- to 14-membered mono-or bi-cyclic heterocyclyl, wherein any alkyl, cycloalkyl or heterocyclyl is optionally unsaturated, or R 4 is (C6-C14)aryl or is (C6-C14)aryl(C1-C6)alkyl, (5- to 14-membered heteroaryl), or (5- to 14-membered heteroaryl)-(C1-C6)alkyl, wherein any alkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl or heteroaryl group is substituted with 0-3 J groups, and wherein any alkyl group can further comprise —O—, —N(R)—, —OC(O)N(R)—, —N(R)C(O)N(R)—, or —OC(O)O— therein; or,

when X is present, R 3 and R 4 together with the carbon atom to which they are bonded can form a (C3-C10) mono- or bicyclic cycloalkyl or 3-10-membered mono- or bicyclic heterocyclyl group or a (C6-C14) aryl group, any of which is substituted with 0-3 J; and

Cyc is a group of formula (II)

wherein

a wavy line indicates a point of bonding; and,

R 7 and R 8 together with the atoms to which they are bonded form a ring such that the group of formula (II) is of formula (IIB)

wherein

a=0, 1, or 2 and c=0, 1, 2, 3, 4, or 5, and the ring is substituted with 0-3 J groups, optionally further comprising within the ring one heteroatom selected from O, NR, and S(O) q wherein q=0, 1, or 2; R 5 and R 6 are each independently H, acyl, or (C1-C6)alkyl, wherein any alkyl is substituted with 0-3 J; or, R 5 and R 6 together with the nitrogen atom to which they are bonded form a 3-9-membered heterocyclyl ring, substituted with 0-3 J groups, and optionally further comprising within the ring one heteroatom selected from O, NR, and S(O) q wherein q=0, 1, or 2, wherein the ring optionally comprises an unsaturation, or is optionally fused with a (C6-C14)aryl substituted with 0-3 J, or both; and,

J is halo, nitro, cyano, R, CF 3 , OR, NR 2 , C(O)OR, C(O)NR 2 , OC(O)OR, OC(O)NR 2 , N(R)C(O)OR, N(R)C(O)NR 2 or thio/thiono analogs thereof; or two J groups together are methylenedioxy or ethylenedioxy; and,

each independently selected R is H, (C1-C6)alkyl, (C1-C6)acyl, (C6-C14)aryl, (C6-C14)aryl(C1-C6)alkyl, or (C6-C14)aroyl, wherein any non-hydrogen R is substituted with 0-3 J R ;

J R is halo, nitro, cyano, CF 3 , OR, NR 2 , C(O)OR, C(O)NR 2 , OC(O)OR, OC(O)NR 2 , N(R)C(O)OR, N(R)C(O)NR 2 or thio/thiono analogs thereof; or two J R groups together are methylenedioxy or ethylenedioxy;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 wherein for the group of formula (IIB), c=0, 1, 2, or 3, and R 5 and R 6 are independently H, methyl, or acyl.

3. A compound of formula (I)

wherein

X is CH 2 or CH 2 CH 2 ,

R 2 is H or methyl,

R 3 is H, and

R 4 is cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, n-heptan-3-yl, 2,6,6,-trimethylcyclohex-1-enyl, 6,6-dimethylbicyclo[3.1.1]hept-2-yl, bicyclo[2.2.1]hept-2-en-5-yl, piperidin-4-yl, tetrahydropyran-4-yl, phenyl, 3-indolyl, 5-benzimidazolyl, 6-indazolyl, 3-quinolyl, 2-naphthyl, 2-benzothiazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, and members of these aryl and heteroaryl groups bering one or more halogen, alkyl, haloalkyl, or alkoxy substitutents;

Cyc is a group of formula (II)

wherein

a wavy line indicates a point of bonding; and,

(a) a=0, 1, 2, 3, 4, or 5; and R 5 , R 6 , R 7 and R 8 are each independently H, (C1-C6)alkyl, or (C1-C6)acyl, wherein any alkyl or acyl is substituted with 0-3 J; or,

(b) R 6 and R 7 together with the atoms to which they are bonded form a heterocyclyl ring such that the group of formula (II) is of formula (IIA)

 wherein

a=0, 1, or 2, and b=0, 1, or 2; optionally further comprising within the heterocyclyl ring 1-2 additional heteroatom independently selected from O, NR, and S(O) q wherein q=0, 1, or 2; and wherein the ring is substituted with 0-3 J groups; R 5 is H, alkyl, cycloalkyl, acyl, or aroyl; and, R 8 is H, alkyl, or cycloalkyl; wherein any non-hydrogen R 5 or R 8 group is substituted with 0-3 J groups; or, R 5 and R 8 can together form a (C3-C5)alkylene bridge; and, wherein the ring optionally comprises an unsaturation, or is optionally fused with a (C6-C14)aryl substituted with 0-3 J, or both; or,

(c) R 7 and R 8 together with the atoms to which they are bonded form a ring such that the group of formula (II) is of formula (IIB)

 wherein

a=0, 1, or 2 and c=0, 1, 2, 3, 4, or 5, and the ring is substituted with 0-3 J groups, optionally further comprising within the ring one heteroatom selected from O, NR, and S(O) q wherein q=0, 1, or 2; R 5 and R 6 are each independently H, acyl, or (C1-C6)alkyl, wherein any alkyl is substituted with 0-3 J; or, R 5 and R 6 together with the nitrogen atom to which they are bonded form a 3-9-membered heterocyclyl ring, substituted with 0-3 J groups, and optionally further comprising within the ring one heteroatom selected from O, NR, and S(O) q wherein q=0, 1, or 2, wherein the ring optionally comprises an unsaturation, or is optionally fused with a (C6-C14)aryl substituted with 0-3 J, or both; and,

J is halo, nitro, cyano, R, CF 3 , OR, NR 2 , C(O)OR, C(O)NR 2 , OC(O)OR, OC(O)NR 2 , N(R)C(O)OR, N(R)C(O)NR 2 or thio/thiono analogs thereof; or two J groups together are methylenedioxy or ethylenedioxy; and,

each independently selected R is H, (C1-C6)alkyl, (C1-C6)acyl, (C6-C14)aryl, (C6-C14)aryl(C1-C6)alkyl, or (C6-C14)aroyl, wherein any non-hydrogen R is substituted with 0-3 J R ;

J R is halo, nitro, cyano, CF 3 , OR, NR 2 , C(O)OR, C(O)NR 2 , OC(O)OR, OC(O)NR 2 , N(R)C(O)OR, N(R)C(O)NR 2 or thio/thiono analogs thereof; or two J R groups together are methylenedioxy or ethylenedioxy;

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 3 in which R 2 is H.

5. A compound wherein the compound has any of the following chemical structures, including all isomeric forms thereof:

6. A pharmaceutical composition comprising a compound of any one of claims 1 , 2 , 3 , 4 , and 5 , and a pharmaceutically acceptable excipient.