Cyclic compounds useful as modulators of TNF α

1. A compound of Formula (I)

or a salt thereof, wherein:

Ring A is 3- to 5-membered carbocyclic ring or 3- to 6-membered heterocyclic ring;

X is CR 1 or N;

Y is —(CR 5 R 5 ) m —;

Z is —(CR 5 R 5 ) n —;

m is zero, 1 or 2;

n is zero, 1 or 2; provided that m+n is zero, 1, or 2;

R 1 is H, halo, —CN, C 1-4 alkyl, C 1-4 haloalkyl, or C 1-4 alkoxy;

R 2 is H, R 1a , C 1-6 haloalkyl, C 2-6 alkenyl substituted with zero to 6 R 1a , C 2-6 alkynyl substituted with zero to 4 R 1a , —(CR g R g ) r (3- to 14-membered carbocyclyl substituted with zero to 3 R 1a ), —(CR g R g ) r (aryl substituted with zero to 3 R 1a ), —(CR g R g ) r (5- to 7-membered heterocyclyl substituted with zero to 3 R 1a ), or —(CR g R g ) r (mono- or bicyclic heteroaryl substituted with zero to 3 R 1a );

R 3 is H, halo, —CN, —CF 3 , —OCF 3 , —NO 2 , C 1-6 alkyl substituted with zero to 6 R 1a , —(CR g R g ) r OR e , —(CR g R g ) r NR c R c , —(CR g R g ) r S(O) p R b , —(CR g R g ) r (3- to 14-membered carbocyclyl substituted with zero to 3 R 1a ), —(CR g R g ) r (aryl substituted with zero to 3 R 1a ), —(CR g R g ) r (5- to 7-membered heterocyclyl substituted with zero to 3 R 1a ), or —(CR g R g ) r (monocyclic or bicyclic heteroaryl substituted with zero to 3 R 1a );

R 4 is H, halo, —CN, C 1-4 alkyl, C 1-4 haloalkyl, or C 1-4 alkoxy;

each R 5 is independently H, halo, —CN, C 1-6 alkyl substituted with zero to 6 R h , C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, —(CR g R g ) r C(O)R b , —(CR g R g ) r C(O)OR b , —(CR g R g ) r C(O)NR c R c , —(CR g R g ) r OR e , —(CR g R g ) r OC(O)R b , —(CR g R g ) r OC(O)NR c R c , —(CR g R g ) r OC(O)OR d , —(CR g R g ) r NR c R c , —(CR g R g ) r NR b C(O)R d , —(CR g R g ) r NR b C(O)OR d , —(CR g R g ) r NR b C(O)NR c R c , —(CR g R g ) r NR b S(O) p R d , —(CR g R g ) r S(O) p R b , —(CR g R g ) r S(O) p NR c R c , —(CR g R g ) r (3- to 14-membered carbocyclyl substituted with zero to 3 R 1a ), —(CR g R g ) r (aryl substituted with zero to 3 R 1a ), —(CR g R g ) r (5- to 7-membered heterocyclyl substituted with zero to 3 R 1a ), or —(CR g R g ) r (mono- or bicyclic heteroaryl substituted with zero to 3 R 1a ); or two R 5 along with the carbon atom to which they are attached form C═O, C═NOR b , or 3- to 6-membered spirocarbocyclic or spiroheterocyclic ring substituted with zero to 3 R i ;

R 6 and R 8 are independently H, halo, —OH, —CN, C 1-5 alkyl, C 1-5 hydroxyalkyl, C 1-5 haloalkyl, C 1-5 alkoxy, —NR x R x , —OC(O)NR x R x , —NR x C(O)OR y , —NR x C(O)R y , —(CR g R g ) r (3- to 14-membered carbocyclyl substituted with zero to 3 R 1a ), —(CR g R g ) r (aryl substituted with zero to 3 R 1a ), —(CR g R g ) r (5- to 10-membered heterocyclyl substituted with zero to 3 R 1a ), or —(CR g R g ) r (mono- or bicyclic heteroaryl substituted with zero to 3 R 1a );

each R 7 is independently halo, —OH, —CN, C 1-5 alkyl, C 1-5 hydroxyalkyl, C 1-5 haloalkyl, —NR x R x , C 1-5 alkoxy, —OC(O)NR x R x , —NR x C(O)OR y , —NR x C(O)R y , —(CR g R g ) r (3- to 14-membered carbocyclyl substituted with zero to 3 R 1a ), —(CR g R g ) r (aryl substituted with zero to 3 R 1a ), —(CR g R g ) r (5- to 10-membered heterocyclyl substituted with zero to 3 R 1a ), or —(CR g R g ) r (mono- or bicyclic heteroaryl substituted with zero to 3 R 1a );

R 9 is —(CR g R g ) r (3- to 14-membered carbocyclyl substituted with zero to 3 R 1a ), —(CR g R g ) r (aryl substituted with zero to 3 R 1a ), —(CR g R g ) r (5- to 10-membered heterocyclyl substituted with zero to 3 R 1a ), or —(CR g R g ) r (mono- or bicyclic heteroaryl substituted with zero to 3 R 1a );

R 10 is H, C 1-6 alkyl, or C 1-6 haloalkyl;

or R 9 and R 10 together with the carbon atom to which they are attached form a 5- to 6-membered spirocarbocyclic or spiroheterocyclic ring, substituted with zero to 6 R i ;

each R 1a is independently F, Cl, Br, —CN, C 1-6 alkyl substituted with zero to 6 R a , C 3-6 cycloalkyl substituted with zero to 6 R a , C 1-3 alkoxy substituted with zero to 6 R a , C 1-3 haloalkoxy, 5- to 7-membered heterocyclyl substituted with zero to 6 R a , aryl substituted with zero to 6 R a , mono- or bicyclic heteroaryl substituted with zero to 6 R a , —C(O)R b , —C(O)OR b , —C(O)NR c R c , —OC(O)R b , —OC(O)NR c R c , —OC(O)OR d , —NR c R c , —NR b C(O)R d , —NR b C(O)OR d , —NR b S(O) p R d , —NR b C(O)NR c R c , —NR b S(O) p NR c R c , —S(O) p R b , —S(O) p NR c R c , or —C(O)NR b (CH 2 ) 1-3 NR c R c ;

each R a is independently halo, —CN, —OH, —NO 2 , —NH 2 , C 1-3 alkyl, C 1-3 fluoroalkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, C 1-3 fluoroalkoxy, —(CH 2 ) r C(O)OH, —C(O)(C 1-3 alkyl), —C(O)O(C 1-4 alkyl), —OC(O)(C 1-3 alkyl), —NH(C 1-3 alkyl), —N(C 1-3 alkyl) 2 , —C(O)NH(C 1-3 alkyl), —OC(O)NH(C 1-3 alkyl), —NHC(O)NH(C 1-3 alkyl), —C(═NH)(NH 2 ), C 3-7 carbocyclyl, aryl, 5- to 7-membered heterocyclyl, mono- or bicyclic heteroaryl, —O(aryl), —O(benzyl), —O(heterocyclyl), —S(O) p (C 1-3 alkyl), —S(O) p (aryl), —S(O) p (heterocyclyl), —NHS(O) 2 (aryl), —NHS(O) 2 (heterocyclyl), —NHS(O) 2 NH(aryl), —NHS(O) 2 NH(heterocyclyl), —NH(aryl), —NH(heterocyclyl), —NHC(O)(aryl), —NHC(O)(C 1-3 alkyl), —NHC(O)(heterocyclyl), —OC(O)(aryl), —OC(O)(heterocyclyl), —NHC(O)NH(aryl), —NHC(O)NH(heterocyclyl), —OC(O)O(C 1-3 alkyl), —OC(O)O(aryl), —OC(O)O(heterocyclyl), —OC(O)NH(aryl), —OC(O)NH(heterocyclyl), —NHC(O)O(aryl), —NHC(O)O(heterocyclyl), —NHC(O)O(C 1-3 alkyl), —C(O)NH(aryl), —C(O)NH(heterocyclyl), —C(O)O(aryl), —C(O)O(heterocyclyl), —N(C 1-3 alkyl)S(O) 2 (aryl), —N(C 1-3 alkyl)S(O) 2 (heterocyclyl), —N(C 1-3 alkyl)S(O) 2 NH(aryl), —N(C 1-3 alkyl)S(O) 2 NH(heterocyclyl), —N(C 1-3 alkyl)(aryl), —N(C 1-3 alkyl)(heterocyclyl), —N(C 1-3 alkyl)C(O)(aryl), —N(C 1-3 alkyl)C(O)(heterocyclyl), —N(C 1-3 alkyl)CO 2 H —N(C 1-3 alkyl)C(O)NH(aryl), —(CH 2 ) 0-3 C(O)NH(heterocyclyl), —OC(O)N(C 1-3 alkyl)(aryl), —OC(O)N(C 1-3 alkyl)(heterocyclyl), —N(C 1-3 alkyl)C(O)O(aryl), —N(C 1-3 alkyl)C(O)O(heterocyclyl), —C(O)N(C 1-3 alkyl)(aryl), —C(O)N(C 1-3 alkyl)(heterocyclyl), —NHS(O) 2 N(C 1-3 alkyl)(aryl), —NHS(O) 2 N(C 1-3 alkyl)(heterocyclyl), —NHP(O) 2 N(C 1-3 alkyl)(aryl), —NHC(O)N(C 1-3 alkyl)(aryl), —NHC(O)N(C 1-3 alkyl)(heterocyclyl), —N(C 1-3 alkyl)S(O) 2 N(C 1-3 alkyl)(aryl), —N(C 1-3 alkyl)S(O) 2 N(C 1-3 alkyl)(heterocyclyl), —N(C 1-3 alkyl)C(O)N(C 1-3 alkyl)(aryl), —N(C 1-3 alkyl)C(O)N(C 1-3 alkyl)(heterocyclyl), or —Si(C 1-3 alkyl) 3 ; or two R a attached to the same carbon atom form ═O;

each R b is independently H, C 1-6 alkyl substituted with zero to 6 R f , C 3-7 cycloalkyl substituted with zero to 6 R f , mono- or bicyclic heterocyclyl substituted with zero to 6 R f , aryl substituted with zero to 3 R f , or mono- or bicyclic heteroaryl substituted with zero to 3 R f ;

each R c is independently H, C 1-6 alkyl substituted with zero to 6 R f , C 3-7 cycloalkyl substituted with zero to 6 R f , mono- or bicyclic heterocyclyl substituted with zero to 6 R f , aryl substituted with zero to 3 R f , or mono- or bicyclic heteroaryl substituted with zero to 3 R f ; or when attached to the same nitrogen, two R c along with the nitrogen atom to which they are attached form 4- to 8-membered heterocyclic ring substituted with zero to 3 R g ;

each R d is independently H, C 1-6 alkyl substituted with zero to 6 R f , C 3-7 cycloalkyl substituted with zero to 6 R f , mono- or bicyclic heterocyclyl substituted with zero to 6 R f , aryl substituted with zero to 3 R f , or mono- or bicyclic heteroaryl substituted with zero to 3 R f ;

each R e is independently H, C 1-6 alkyl substituted with zero to 6 R f , C 1-3 haloalkyl, C 3-7 cycloalkyl substituted with zero to 6 R f , mono- or bicyclic heterocyclyl substituted with zero to 6 R f , aryl substituted with zero to 3 R f , or mono- or bicyclic heteroaryl substituted with zero to 3 R f ;

each R f is independently H, halo, —OH, —CN, C 1-6 alkyl substituted with zero to 6 R a , C 1-3 alkoxy, C 3-7 cycloalkyl substituted with zero to 6 R a , mono- or bicyclic heterocyclyl substituted with zero to 6 R a , aryl substituted with zero to 3 R a , or mono- or bicyclic heteroaryl substituted with zero to 3 R a ;

each R g is independently H, F, —OH, —CN, C 1-3 alkyl, —CF 3 , or phenyl;

each R h is independently —OH or halo;

each R i is independently H, halo, —CN, —OH, C 1-3 alkyl, C 1-3 fluoroalkyl, or C 1-3 alkoxy; or two R i attached to the same carbon atom of the spirocarbocyclic or spiroheterocyclic ring, form ═O; or two R i attached to neighboring carbon atoms of the spirocarbocyclic or spiroheterocyclic ring, form a benzo ring along with the carbon atoms to which they are attached, said benzo ring substituted with zero to 4 R f ;

each R x is independently H or C 1-5 alkyl;

each R y is independently C 1-5 alkyl;

each p is independently zero, 1, or 2;

q is zero, 1, or 2; and

each r is independently zero, 1, 2, 3, or 4.

2. The compound according to claim 1 or a salt thereof, wherein:

m+n is zero or 1.

3. The compound according to claim 1 or a salt thereof, wherein:

Ring A is a 3- to 6-heterocyclic ring.

4. The compound according to claim 1 or a salt thereof, wherein:

m+n is zero or 1; and

Ring A is 3- to 5-membered carbocyclic ring.

5. The compound according to claim 1 or a salt thereof,

wherein:

Ring A is a 3-membered carbocyclic ring;

m+n is zero;

X is CR 1 ;

R 1 is H;

R 2 is Br; or phenyl, pyridinyl, pyrimidinyl or dihydropyridinyl, each substituted with —CN, —C(O)NH 2 , —C(O)NH(CH 3 ), —C(O)OC(CH 3 ) 3 , —C(CH 3 ) 20 H, —CH 2 C(CH 3 ) 20 H, —CH 2 C(O)OH, —S(O) 2 NH 2 , morpholinyl, hydroxyoxetanyl, dioxothiomorpholinyl, carboxymethylpiperazinyl, and piperazinonyl;

R 3 is F;

R 4 is H;

R 6 is H; and

R 7 is phenyl;

R 8 is H;

R 10 is H; and

q is zero or 1.

6. The compound according to claim 1 or a salt thereof,

wherein:

Ring A is a 5-membered heterocyclic ring;

m+n is zero;

X is CR 1 ;

R 1 is H;

R 2 is methoxypyridinyl;

R 3 is H;

R 4 is H;

R 6 is H;

R 8 is H; and

R 9 is phenyl.

7. The compound according to claim 1 or a salt thereof, wherein said compound is: rac-2-(5-((1aR,8R,8aS)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyrimidin-2-yl)propan-2-ol (1); 2-(5-((1 aR,8R,8aS)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a] imidazol-5-yl)pyrimidin-2-yl)propan-2-ol (2); 2-(5-((1aS,8S,8aR)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyrimidin-2-yl) propan-2-ol (3); 2-(4-(5-((1aR,8R,8aS)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyrimidin-2-yl)piperazin-1-yl)acetic acid (4); 4-((1aR,8R,8aS)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)benzenesulfonamide (5); 4-(5-((1aR,8R,8aS)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyrimidin-2-yl)morpholine (6); 5-((1aR,8R,8aS)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)picolinamide (7); 5-((1aR,8R,8aS)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)-N-methylpicolinamide (8); 4-(5-((1aR,8R,8aS)-8-(2-(difluoromethoxy) phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl) pyrimidin-2-yl)piperazin-2-one (9); 5-((1aR,8R,8aS)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)picolinonitrile (10); rac-(1aR,8S,8aS)-5-bromo-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazole (11); 2-(4-((1aR,8R,8aS)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)phenyl)propan-2-ol (12); 2-(5-((1aR,8R,8aS)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyridin-2-yl)propan-2-ol (13); 3-(5-((1aR,8R,8aS)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyrimidin-2-yl)oxetan-3-ol (14); 4-(5-((1aR,8R,8aS)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyrimidin-2-yl) thiomorpholine 1,1-dioxide (15); 1-(4-((1aR,8R,8aS)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)-1H-pyrazol-1-yl)-2-methylpropan-2-ol (16); tert-butyl 4-((1aR,8R,8aS)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)-3,6-dihydropyridine-1(2H)-carboxylate (17); 2-(4-(5-((1aS,8S,8aR)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyrimidin-2-yl)piperazin-1-yl)acetic acid (18); 5-((1aS,8S,8aR)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)picolinamide (19); rac-2-(5-((1aR,8S,8aS)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyrimidin-2-yl)propan-2-ol (20); 2-(5-((1aS,8R,8aR)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyrimidin-2-yl) propan-2-ol (21); 5-((1aS,8R,8aR)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)picolinamide (22); rac-2-(5-((1aR,8S,8aS)-8-(2-(benzyloxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyrimidin-2-yl)propan-2-ol (25); rac-2-(5-((1aR,8R,8aS)-8-(2-(benzyloxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyrimidin-2-yl)propan-2-ol (26); 4-(5-((1aS,8R,8aR)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyrimidin-2-yl)morpholine (31); 4-(5-((aS,8S,8aR)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyrimidin-2-yl)morpholine (32); 2-(4-(5-((1aS,8R,8aR)-8-(2-(difluoromethoxy)phenyl)-4-fluoro-1, a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyrimidin-2-yl)piperazin-1-yl)acetic acid (33); 2-(5-((1aS,8R,8aR)-4-fluoro-8-(2-(pyridin-4-ylmethoxy)phenyl)-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyrimidin-2-yl)propan-2-ol (34); 2-(5-((1aS,8S,8aR)-4-fluoro-8-(2-(pyridin-4-ylmethoxy) phenyl)-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)pyrimidin-2-yl)propan-2-ol (35); rac-(3aR,10S,10aS)-7-(6-methoxypyridin-3-yl)-10-phenyl-1,2,3,3a,10,10a-hexahydrobenzo[d]pyrrolo[3′,4′:3,4]pyrrolo[1,2-a]imidazole (36); or rac-5-((1R,1aS,8S,8aR)-8-(2,5-dimethylphenyl)-1-phenyl-1,1a,8,8a-tetrahydrobenzo[d]cyclopropa[3,4]pyrrolo[1,2-a]imidazol-5-yl)-N-methylpicolinamide (43).

8. A pharmaceutical composition comprising one or more compounds according to claim 1 or a salt thereof; and a pharmaceutically acceptable carrier or diluent.

9. A method for inhibiting or relieving a disease comprising the administration to a subject in need thereof a therapeutically-effective amount of at least one compound according to claim 1 , wherein said disease is an inflammatory or autoimmune disease selected from Crohn's disease, ulcerative colitis, asthma, rheumatoid arthritis, systemic lupus erythematosus, lupus nephritis, cutaneous lupus, psoriasis, systemic onset juvenile idiopathic arthritis, multiple sclerosis, gout, and gouty arthritis.

10. The method according to claim 9 , wherein the disease is selected from Crohn's disease, ulcerative colitis, systemic lupus erythematosus, lupus nephritis, cutaneous lupus, and psoriasis.