Substituted 1,3-dihydro-imidazol-2-one and 1,3-dihydro-imidazol-2-thione derivatives as inhibitors of matrix metalloproteinases and/or TNF-alpha converting enzyme (TACE)

• US 20050075384A1
• Filed: 09/21/2004
• Published: 04/07/2005
• Est. Priority Date: 10/01/2003
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Gilmore, John L., Sheppeck, James
• Granted Patent: US 7,211,671 B2
• Time in Patent Office: Days
• US Class Current: 514/389
• CPC Class Codes: C04B 35/632 Organic additives
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links

Abstract

The present invention describes novel 1,3-dihydro-imidazol-2-one or 1,3-dihydro-imidazol-2-thione compounds of formula (I):
or a stereoisomer or pharmaceutically acceptable salt or solvate thereof, wherein A, L R¹, R², R³ and R⁴ are defined in the present specification, which are useful as selective inhibitors of MMP, TACE, aggrecanase or a combination thereof. This invention also relates to pharmaceutical compositions comprising these compounds and methods of using the same.

Claims

1. A compound of Formula (I):

2. A compound according to claim 1, wherein:

R¹ is Q, F, Cl, Br, I, CN, NO₂, —

CF₂CF₃, —

NR⁷R⁸, C_1-4 haloalkyl, —

C_1-6 alkylene-Q, —

C_2-6 alkenylene-Q, —

C_2-6 alkynylene-Q, —

(CR^aR^a1)_tO(CR^aR^a1)_s-Q, —

(CR^aR^a1)_tNR^a(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rC(O)(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rC(O)O(CR^aR^a1)_s-Q, —

(CR^aR^a1)_tOC(O)(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rC(O)NR^aR^a1, —

(CR^aR^a1)_rC(O)NR^a(CR^aR^a1)_s-Q, —

(CR^aR^a1)_tNR^aC(O)(CR^aR^a1)_s-Q, —

(CR^aR^a1)_tS(CR^aR^a1)_s-Q, —

(CR^aR^a1)_tS(O)(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rS(O)₂(CR^aR^a1)_s-Q, —

(CR^aR^a1)_tSO₂NR^a(CR^aR^a1)_s-Q, or —

(CR^aR^a1)_tNR^aSO₂(CR^aR^a1)_s-Q;

R⁵ is Q, —

C_1-6 alkylene-Q, —

C_2-6 alkenylene-Q, —

C_2-6 alkynylene-Q, —

(CR^aR^a1)_tO(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rNR^a(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rC(O)(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rC(O)O(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rOC(O)(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rC(O)NR^aR^a1, —

(CR^aR^a1)_rC(O)NR^a(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rNR^aC(O)(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rS(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rS(O)(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rS(O)₂(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rSO₂NR^a(CR^aR^a1)_s-Q, or —

(CR^aR^a1)_rNR^aSO₂(CR^aR^a1)_s-Q;

R⁶ is H, —

C_1-6 alkylene-Q, —

C_2-6 alkenylene-Q, or —

C_2-6 alkynylene-Q;

each R⁹ is, independently at each occurrence, H, —

(CR^aR^a1)_tNR^aR^a1, —

(CR^aR^a1)_rC(O)NR^aOH, —

(CR^aR^a1)_rC(O)(CR^aR^a1)_sR^e, —

(CR^aR^a1)_rC(O)OR^a1, —

(CR^aR^a1)_rC(O)NR^aR^a1, —

(CR^aR^a1)_tNR^aC(O)R^a1, —

(CR^aR^a1)_tNR^aC(O)NR^aR^a1, —

(CR^aR^a1)_tS(O)R^a3, —

(CR^aR^a1)_tS(O)R^a3, —

(CR^aR^a1)_rS(O)₂R^a3, —

(CR^aR^a1)SO₂NR^aR^a1, —

(CR^aR^a1)_tNR^aSO₂R^a3, C_1-6 alkyl substituted with 0-2 R^c1, C_2-6 alkenyl substituted with 0-2 R^c1, C_2-6 alkynyl substituted with 0-2 R^c1, —

(CR^aR^a1)_r—

C_3-10 carbocycle substituted with 0-2 R^c1;

or (CR^aR^a1)_r-5-10 membered heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)_p, and substituted with 0-2 R^c1;

each R¹⁰ is, independently at each occurrence, H, —

(CR^aR^a1)_rNR^aR^a1, —

(CR^aR^a1)_rC(O)NR^aOH, —

(CR^aR^a1)_rC(O)(CR^aR^a1)_sR^e, —

(CR^aR^a1)_rC(O)OR^a1, —

(CR^aR^a1)_rC(O)NR^aR^a1, —

(CR^aR^a1)_rNR^aC(O)R^a1, —

(CR^aR^a1)_rNR^aC(O)NR^aR^a1, —

(CR^aR^a1)_rS(O)R^a3, —

(CR^aR^a1)_rS(O)R^a3, —

(CR^aR^a1)_rS(O)₂R^a3, —

(CR^aR^a1)_rSO₂NR^aR^a1, —

(CR^aR^a1)_rNR^aSO₂R^a3, C_1-6 alkyl substituted with 0-2 R^c1, C_2-6 alkenyl substituted with 0-2 R^c1, C_2-6 alkynyl substituted with 0-2 R^c1, —

(CR^aR^a1)_r—

C_3-10 carbocycle substituted with 0-2 R^c1;

or —

(CR^aR^a1)_r-5-10 membered heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)_p, and substituted with 0-2 R^c1;

each Q is, independently at each occurrence, H, CF₃, —

CH₂F, —

CHF₂, C_1-6 alkyl, a C_3-10 carbocycle substituted with 0-5 R^d, or a 5-10 membered heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of NR⁹, O, and S(O)_p, and substituted with 0-5 R^d;

each Q¹ is, independently at each occurrence, C_1-6 alkyl, a C_3-10 carbocycle substituted with 0-5 R^d, or a 5-12 membered heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of NR⁹, O, and S(O)_p, and substituted with 0-5 R^d;

Z⁰ is aryl or a 5-6 membered heteroaryl consisting of carbon atoms and 0-3 ring heteroatoms selected from O, N, NR⁹, and S, and substituted with 0-3 R¹⁰; and

the aryl or heteroaryl is optionally fused to a 5-6 membered carbocycle or heterocycle consisting of carbon atoms and 0-2 ring heteroatoms selected from O, N, NR⁹, and S(O)_p, and 0-2 double bonds, and substituted with 0-3 R¹⁰;

W is (CR^aR^a1)_m, C_2-3 alkenylene, or C_2-3 alkynylene;

U is O, C(O), CR^a(OH), C(O)O, OC(O), C(O)NR^a1, NR^a1C(O), S(O)_p, S(O)_pNR^a1, or NR^a1S(O)_p;

X is a bond or C_1-3 alkylene;

Y is a bond, O, NR^a1, S(O)_p, or C(O);

alternatively, Z⁰ is absent, and W—

U—

X—

Y forms S(O)_p;

Z is a C_3-8 cycloalkyl substituted with 0-5 R^b, a C_3-8 cycloalkenyl substituted with 0-5 R^b, phenyl substituted with 0-5 R^b, naphthyl substituted with 0-5 R^b or a 5-14 membered heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)_p and substituted with 0-5 R^b;

U^a is a bond, O, NR^a1, C(O), CR^a(OH), C(O)O, C(O)NR^a1, NR^a1C(O), S(O)_p, S(O)_pNR^a1, or NR^a1S(O)_p;

X^a is a bond, C_1-4 alkylene, C_2-4 alkenylene, or C_2-4 alkynylene;

Y^a is a bond, O, or NR^a1;

Z^a is a C_6-13 carbocycle substituted with 0-5 R^c, or a 5-14 membered heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)_p and substituted with 0-5 R^c;

provided that U, Y, Z, U^a, Y^a, and Z^a do not combine to form a N—

N, N—

O, O—

N, O—

O, S(O)_p—

O, O—

S(O)_p or S(O)_p—

S(O)_p group;

each R^c is, independently at each occurrence, H, Cl, F, Br, I, ═

O, CN, NO₂, CF₃, CF₂CF₃, CH₂F, CHF₂, —

(CR^aR^a1)_rOR^a, —

(CR^aR^a1)_rNR^aR^a1, —

(CR^aR^a1)_rC(O)NR^aOH, —

(CR^aR^a1)_rC(O)R^a1, —

(CR^aR^a1)_rC(O)OR^a1, —

(CR^aR^a1)_rC(O)NR^aR^a1, —

(CR^aR^a1)_rNR^aC(O)R^a1, —

(CR^aR^a1)_rS(O)_pR^a3, —

(CR^aR^a1)_rSO₂NR^aR^a1, —

(CR^aR^a1)_rNR^aSO₂R^a3, C_1-6 alkyl substituted with 0-1 R^c1, C_2-6 alkenyl substituted with 0-1 R^c1, C_2-6 alkynyl substituted with 0-1 R^c1, —

(CH₂)_r—

C_3-6 carbocycle substituted with 0-2 R^c1, or —

(CH₂)_r-5-6 membered heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)_p, and substituted with 0-2 R^c1;

alternatively, when two R^c groups are attached to the same carbon atom, they form a 3-8 membered carbocyclic or heterocyclic spiro ring C substituted with 0-2 R^c1 and consisting of carbon atoms, 0-4 ring heteroatoms selected from O, N, and S(O)_p, and 0-2 double bonds, provided that ring C contains other than a S—

S, O—

O, or S—

O bond;

alternatively, when two R^c groups are attached to adjacent carbon atoms, together with the carbon atoms to which they are attached they form a 5-7 membered carbocyclic or heterocyclic ring D substituted with 0-2 R^c1 and consisting of carbon atoms, 0-2 heteroatoms selected from the group consisting of N, O, and S(O)_p, and 0-3 double bonds; and

each R^d is, independently at each occurrence, C_1-6 alkyl, OR^a, Cl, F, Br, I, ═

O, CN, NO₂, NR^aR^a1, C(O)R^a, —

C(O)OR^a, —

C(O)NR^aR^a1, —

S(O)₂NR^aR^a1, —

NR^aS(O)₂R^a3, —

S(O)_pR^a3, CF₃, C_3-6 carbocycle, or a 5-6 membered heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)_p.

3. A compound according to claim 2, wherein:

R¹ is Q, F, Cl, CN, —

NR⁷R⁸, C_1-4 haloalkyl, —

C_1-4 alkylene-Q, —

C_2-4 alkenylene-Q, —

C_2-4 alkynylene-Q, —

(CR^aR^a1)_tO(CR^aR^a1)_s-Q, —

(CR^aR^a1)_tNR^a(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rC(O)(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rC(O)O(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rC(O)NR^aR_a1, —

(CR^aR^a1)_rC(O)NR_a(CR^aR^a1)_s-Q, —

(CR^aR^a1)_tS(CR^aR^a1)_s-Q, —

(CR^aR^a1)_tS(O)(CR^aR^a1)_s-Q, —

(CR^aR^a1)_rS(O)₂(CR^aR^a1)_s-Q, —

(CR^aR^a1)_tSO₂NR^a(CR^aR^a1)_s-Q, or —

(CR^aR^a1)_tNR^aSO₂(CR^aR^a1)_s-Q;

R² is H or C_1-4 alkyl;

R³ is H or C_1-4 alkyl;

R⁵ is Q, C_1-4 alkyl, C_2-4 alkenyl, C_2-4 alkynyl, —

(CH₂)_tO(CH₂)_s-Q, —

(CH₂)_rNR^a(CH₂)_s-Q, —

(CH₂)_rC(O)(CH₂)_s-Q, —

(CH₂)_rC(O)O(CH₂)_s-Q, —

(CH₂)_rOC(O)(CH₂)_s-Q, —

(CH₂)_rC(O)NR^aR^a1, —

(CH₂)_rC(O)NR^a(CH₂)_s-Q, —

(CH₂)_rNR^aC(O)(CH₂)_s-Q, —

(CH₂)_rS(CH₂)_s-Q, —

(CH₂)_rS(O)(CH₂)_s-Q, —

(CH₂)_rS(O)₂(CH₂)_s-Q, —

(CH₂)_rSO₂NR^a(CH₂)_s-Q, or —

(CH₂)_rNR^aSO₂(CH₂)_s-Q;

R⁶ is H, —

C_1-4 alkyl, C_2-4 alkenyl, or C_2-4 alkynyl;

R⁷ is H, C_1-4 alkyl, C_2-4 alkenyl, C_2-4 alkynyl, —

(CR^aR^a1)_rC(O)(CR^aR^a1)_s-Q¹, —

(CR^aR^a1)_rC(O)O(CR^aR^a1)_s-Q¹, —

(CR^aR^a1)_rC(O)O(CR^aR^a1)_tOC(O)_s-Q¹, —

(CR^aR^a1)_rC(O)NH(CR^aR^a1)_s-Q¹, or —

(CR^aR^a1)_rS(O)₂)(CR^aR^a1)_s-Q¹;

R⁸ is H, C_1-4 alkyl, or —

(CH₂)_n-phenyl;

each R⁹ is, independently at each occurrence, H, —

(CR^aR^a1)_tNR^aR^a1, —

(CR^aR^a1)_rC(O)NR^aOH, —

(CR^aR^a1)_rC(O)(CR^aR^a1)_sR^e, —

(CR^aR^a1)_rC(O)OR^a1, —

(CR^aR^a1)_rC(O)NR^aR^a1, —

(CR^aR^a1)_tNR^aC(O)R^a1, —

(CR^aR^a1)_tS(O)R^a3, —

(CR^aR^a1)_tS(O)R^a3, —

(CR^aR^a1)_rS(O)₂R^a3, —

(CR^aR^a1)SO₂NR^aR^a1, —

(CR^aR^a1)_tNR^aSO₂R^a3, C_1-4 alkyl substituted with 0-1 R^c1, C_2-4 alkenyl substituted with 0-1 R^c1, C_2-4 alkynyl substituted with 0-1 R^c1, —

(CH₂)_r—

C_3-10 carbocycle substituted with 0-2 R^c1;

or —

(CH₂)_r-5-10 membered heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)_p, and substituted with 0-2 R^c1;

each R¹⁰ is, independently at each occurrence, H, —

(CR^aR^a1)_rNR^aR^a1, —

(CR^aR^a1)_rC(O)NR^aOH, —

(CR^aR^a1)_rC(O)(CR^aR^a1)_sR^e, —

(CR^aR^a1)_rC(O)OR^a1, —

(CR^aR^a1)_rC(O)NR^aR^a1, —

(CR^aR^a1)_rNR^aC(O)R^a1, —

(CR^aR^a1)_rS(O)R^a3, —

(CR^aR^a1)_rS(O)R^a3, —

(CR^aR^a1)_rS(O)₂R^a3, —

(CR^aR^a1)_rSO₂NR^aR^a1, —

(CR^aR^a1)_rNR^aSO₂R^a3, C_1-4 alkyl substituted with 0-1 R^c1, C_2-4 alkenyl substituted with 0-1 R^c1, C_2-4 alkynyl substituted with 0-1 R^c1, —

(CH₂)_r—

C_3-10 carbocycle substituted with 0-2 R^c1;

or —

(CH₂)_r-5-10 membered heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)_p, and substituted with 0-2 R^c1;

Z⁰ is phenyl substituted with 0-3 R¹⁰, or a 5-6 membered heteroaryl substituted with 0-3 R¹⁰ and selected from;

oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrrolyl, furanyl, thienyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, or pyrazolyl;

W is (CH₂)_m;

U is O, C(O), CR^a(OH), C(O)NR^a1, NR^a1C(O), S(O)_p, S(O)_pNR^a1, or NR^a1S(O)_p;

X is a bond, or methylene or ethylene;

Y is a bond, O, NR^a1, S(O)_p, or C(O);

alternatively, Z⁰ is absent, and W—

U—

X—

Y forms S(O)_p;

U^a is a bond, O, NR^a1, C(O), C(O)NR^a1, NR^a1C(O), S(O)_p, S(O)_pNR^a1, or NR^a1S(O)_p;

each R^c is, independently at each occurrence, H, Cl, F, Br, I, ═

O, CN, NO₂, CF₃, CH₂F, CHF₂, —

(CR^aR^a1)_rOR^a, —

(CR^aR^a1)_rNR^aR^a1, —

(CR^aR^a1)_rC(O)R^a1, —

(CR^aR^a1)_rC(O)OR^a1, —

(CR^aR^a1)_rC(O)NR^aR^a1, —

(CR^aR^a1)_rNR^aC(O)R^a1, —

(CR^aR^a1)_rS(O)_pR^a3, —

(CR^aR^a1)_rSO₂NR^aR^a1, —

(CR^aR^a1)_rNR^aSO₂R^a3, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, —

(CH₂)_r—

C_3-6 cycloalkyl substituted with 0-1 R^c1, phenyl substituted with 0-2 R^c1, or —

(CH₂)_r-5-6 membered heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)_p, and substituted with 0-2 R^c1;

alternatively, when two R^c groups are attached to adjacent carbon atoms, together with the carbon atoms to which they are attached they form a 5-7 membered carbocyclic or heterocyclic ring D substituted with 0-2 R^c1 and consisting of carbon atoms, 0-2 heteroatoms selected from the group consisting of N, O, and S(O)_p, and 0-3 double bonds;

each R^d is, independently at each occurrence, C_1-6 alkyl, OR^a, Cl, F, Br, I, ═

O, NR^aR^a1, C(O)R^a, —

C(O)OR^a, —

C(O)NR^aR^a1, —

S(O)₂NR^aR^a1, —

NR^aS(O)₂R^a3, —

S(O)_pR^a3, CF₃, or phenyl;

m is 0, 1, or 2;

n is 0, 1, or 2;

each r is, independently at each occurrence, 0, 1, 2, or 3;

each s is, independently at each occurrence, 0, 1, 2, or 3; and

each t is, independently at each occurrence, 2, or 3.

4. A compound according to claim 3, wherein:

A is O;

R¹ is Q, F, Cl, CN, —

NR⁷R⁸, C_1-4 haloalkyl, —

C_1-4 alkylene-Q, —

C_2-4 alkenylene-Q, —

C_2-4 alkynylene-Q, —

(CH₂)_tO(CH₂)_s-Q, —

(CH₂)_tNR^a(CH₂)_s-Q, —

(CH₂)_rC(O)(CH₂)_s-Q, —

(CH₂)_rC(O)O(CH₂)_s-Q, —

(CH₂)_rC(O)NR^aR^a1, —

(CH₂)_rC(O)NR^a(CH₂)_s-Q, —

(CH₂)_tS(CH₂)_s-Q, —

(CH₂)_tS(O)(CH₂)_s-Q, —

(CH₂)_rS(O)₂(CH₂)_s-Q, —

(CH₂)_tSO₂NR^a(CH₂)_s-Q, or —

(CH₂)_tNR^aSO₂(CH₂)_s-Q;

R⁵ is H, C_1-4 alkyl, C_2-4 alkenyl, or C_2-4 alkynyl;

R⁷ is H, C_1-4 alkyl, or —

(CH₂)_n-phenyl;

R⁸ is H, C_1-4 alkyl, or —

(CH₂)_n-phenyl;

each R⁹ is, independently at each occurrence, H, —

(CH₂)_tNR^aR^a1, —

(CH₂)_rC(O)(CH₂)_sR^e, —

(CH₂)_rC(O)OR^a1, —

(CH₂)_rC(O)NR^aR^a1, —

(CH₂)_tNR^aC(O)R^a1, —

(CH₂)_tS(O)R^a3, —

(CH₂)_tS(O)R^a3, —

(CH₂)_rS(O)₂R^a3, —

(CH₂)SO₂NR^aR^a1, —

(CH₂)_tNR^aSO₂R^a3, C_1-4 alkyl, or —

(CH₂)_n-phenyl;

each R¹⁰ is, independently at each occurrence, H, —

(CH₂)_rNR^aR^a1, —

(CH₂)_rC(O)(CH₂)_sR^e, —

(CH₂)_rC(O)OR^a1, —

(CH₂)_rC(O)NR^aR^a1, —

(CH₂)_rNR^aC(O)R^a1, —

(CH₂)_rS(O)R^a3, —

(CH₂)_rS(O)R^a3, —

(CH₂)_rS(O)₂R^a3, —

(CH₂)_rSO₂NR^aR^a1, —

(CH₂)_tNR^aSO₂R^a3, C_1-4 alkyl, or —

(CH₂)_n-phenyl;

Z⁰ is phenyl substituted with 0-2 R¹⁰, or pyridyl substituted with 0-2 R¹⁰;

alternatively, Z⁰ is absent, and W—

U—

X—

Y forms S(O)_p;

U is O, C(O), CH(OH), C(O)NH, NHC(O), S(O)_p, S(O)_pNH, or NHS(O)_p;

Z is a C_4-8 cycloalkyl substituted with 0-3 R^b, a C_4-8 cycloalkenyl substituted with 0-3 R^b, phenyl substituted with 0-4 R^b, naphthyl substituted with 0-5 R^b, or a heterocycle substituted with 0-3 R^b and selected from the group;

furanyl, tetrahydrofuranyl, thiazolyl, oxazolyl, imidazolyl, isothiazolyl, isoxazolyl, 4,5-dihydro-isoxazolyl, thienyl, triazolyl, thiadiazolyl, oxadiazolyl, pyridyl, pyrimidinyl, piperazinyl, piperidinyl, pyranyl, pyrazinyl, pyrazolyl, pyridoimidazolyl, pyrrolidinyl, pyrrolyl, indolyl, indolinyl, benzimidazolyl, benzothiazinyl, benzofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benzisoxazolyl, benzisothiazolyl, quinolinyl, tetrahydroquinolinyl, isoquinolinyl, tetrahydro-isoquinolinyl, indazolyl, isobenzofuranyl, isoindazolyl, isoindolinyl, isoindolyl, methylenedioxyphenyl, and quinazolinyl;

Z^a is phenyl substituted with 0-3 R^c, naphthyl substituted with 0-3 R^c, or a heterocycle substituted with 0-3 R^c and selected from the group;

furanyl, tetrahydrofuranyl, thiazolyl, oxazolyl, imidazolyl, isothiazolyl, isoxazolyl, 4,5-dihydro-isoxazolyl, thienyl, triazolyl, thiadiazolyl, oxadiazolyl, pyridyl, pyrimidinyl, piperazinyl, piperidinyl, pyranyl, pyrazinyl, pyrazolyl, pyridoimidazolyl, pyrrolidinyl, pyrrolyl, indolyl, indolinyl, benzimidazolyl, benzothiazinyl, benzofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benzisoxazolyl, benzisothiazolyl, quinolinyl, tetrahydroquinolinyl, isoquinolinyl, tetrahydro-isoquinolinyl, indazolyl, isobenzofuranyl, isoindazolyl, isoindolinyl, isoindolyl, methylenedioxyphenyl, quinazolinyl, 1,1-dioxido-2,3-dihydro-4H-1,4-benzothiazin-4-yl, 1,1-dioxido-3,4-dihydro-2H-1-benzothiopyran-4-yl, 3,4-dihydro-2H-chromen-4-yl, 2H-chromen-4-yl, and pyrazolo[1,5-a]pyridinyl;

each R^c is, independently at each occurrence, H, Cl, F, Br, ═

O, CF₃, CH₂F, CHF₂, —

(CR^aR^a1)_rOR^a, —

(CR^aR^a1)_rNR^aR^a1, —

(CR^aR^a1)_rC(O)R^a1, —

(CR^aR^a1)_rC(O)OR^a1, —

(CR^aR^a1)_rC(O)NR^aR^a1, —

(CR^aR^a1)_rNR^aC(O)R^a1, —

(CR^aR^a1)_rS(O)_pR^a3, —

(CR^aR^a1)_rSO₂NR^aR^a1, —

(CR^aR^a1)_rNR^aSO₂R^a3, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, phenyl substituted with 0-2 R^c1, or a 5-6 membered heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)_p, and substituted with 0-2 R^c1;

alternatively, when two R^c groups are attached to adjacent carbon atoms, together with the carbon atoms to which they are attached they form a 5-6 membered carbocyclic or heterocyclic ring D substituted with 0-2 R^c1 and consisting of carbon atoms, 0-2 heteroatoms selected from the group consisting of N, O, and S(O)_p, and 0-3 double bonds; and

each R^d is, independently at each occurrence, C_1-6 alkyl, OR^a, Cl, F, Br, I, ═

O, NR^aR^a1, C(O)R^a, —

C(O)OR^a, —

C(O)NR^aR^a1, —

S(O)₂NR^aR^a1, —

NR^aS(O)₂R^a3, —

S(O)_pR^a3, CF₃, or phenyl.

5. A compound according to claim 4, wherein:

A is O;

L is a bond, CO or CH₂;

R¹ is H, C_1-4 haloalkyl, C_1-4 alkyl, or —

C(O)O(CH₂)_s-H;

Z⁰ is phenyl;

alternatively, Z⁰ is absent, and W—

U—

X—

Y forms S(O)_p;

Z is phenyl substituted with 0-2 R^b;

Z^a is phenyl substituted with 0-3 R^c, naphthyl substituted with 0-3 R^c, or a heterocycle substituted with 0-3 R^c and selected from the group;

pyridyl, quinolinyl, imidazolyl, benzimidazolyl, indolyl, 1,1-dioxido-2,3-dihydro-4H-1,4-benzothiazin-4-yl, 1,1-dioxido-3,4-dihydro-2H-1-benzothiopyran-4-yl, 3,4-dihydro-2H-chromen-4-yl, 2H-chromen-4-yl, pyrazolyl, and pyrazolo[1,5-a]pyridinyl;

each R^b is, independently at each occurrence, C_1-6 alkyl, —

OR^a, Cl, F, Br, —

NR^aR^a1, —

C(O)R^a, —

C(O)OR^a, —

C(O)NR^aR^a1, —

S(O)₂NR^aR^a1, —

NR^aS(O)₂R^a3, —

S(O)_pR^a3, or CF₃;

each R^c is, independently at each occurrence, H, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, Cl, F, Br, ═

O, CF₃, —

(CH₂)_rOR^a, —

(CH₂)_rNR^aR^a1, —

(CH₂)_rC(O)R^a1, —

(CH₂)_rC(O)OR^a1, —

(CH₂)_rC(O)NR^aR^a1, —

(CH₂)_rNR^aC(O)R^al, —

(CH₂)_rS(O)_pR^a3, —

(CH₂)_rSO₂NR^aR^a1, or —

(CH₂)_rNR^aSO₂R^a3;

alternatively, when two R^c groups are attached to adjacent carbon atoms, together with the carbon atoms to which they are attached they form a 5-6 membered carbocyclic or heterocyclic ring consisting of;

carbon atoms and 0-1 heteroatoms selected from the group consisting of N, O, and S(O)_p; and

each R^e is, independently at each occurrence, H, C_1-6 alkyl, C_1-6 alkoxy, phenoxy, benzoxy, phenyl substituted with 0-1 R^c1, or a 5-6 membered heterocycle consisting of carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)_p, and substituted with 0-1 R^c1.

6. A compound according to claim 1, wherein the compound is selected from the group:

4-(2-methyl-quinolin-4-yl methoxy)-N-[2-(2-oxo-2,3-dihydro-1H-imidazole-4-carbonyl)phenyl]benzamide;

4-(2-methyl-quinolin-4-yl methyl)-N-[2-(2-oxo-2,3-dihydro-1H-imidazole-4-carbonyl)phenyl]benzamide;

4-(2-methyl-quinolin-4-yl methoxy)-N-[2-(2-oxo-2,3-dihydro-1H-imidazol-4-yl methyl)phenyl]benzamide;

5-[4-(2-methyl-quinolin-4-ylmethoxy)-benzenesulfonylmethyl]-2-oxo-2,3-dihydro-1H-imidazole-4-carboxylic acid methyl ester;

4-[4-(2-methyl-quinolin-4-ylmethoxy)-phenylsulfanylmethyl]-1,3-dihydro-imidazol-2-one;

4-[4-(2-methyl-quinolin-4-ylmethoxy)-benzenesulfinylmethyl]-1,3-dihydro-imidazol-2-one; and

4-[4-(2-Methyl-quinolin-4-ylmethoxy)-benzenesulfonylmethyl]-1,3-dihydro-imidazol-2-one;

or a stereoisomer or pharmaceutically acceptable salt or solvate thereof.

7. A pharmaceutical composition, comprising:

a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 1, or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof.

8. A method for treating an inflammatory disorder, comprising:

administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1 or a stereoisomer or pharmaceutically acceptable salt or solvate thereof.

9. A method of treating according to claim 8, wherein the disease or condition is selected from to as allergy, allergic asthma, autoimmune disease, chronic obstruction pulmonary disease, corneal ulceration, Crohn'"'"'s disease, fever, gingivitis, gout, infectious arthritis, inflammation, osteoarthritis, pelvic inflammatory disease, periodontitis, psoriasis, psoriatic arthritis, pulmonary emphysema, rheumatic fever, rheumatoid arthritis, skin inflammatory diseases, and ulcerative colitis.