Hydantoin compounds

1. A compound of formula I:

wherein:

Q is methylene or ethylene;

R 1 is C 1-6 alkoxy, C 1-8 hydroxyalkyl, (C 1-3 alkoxy)C 1-3 alkyl, C 1-3 alkylthio, C 2-5 alkenyl, phenyl, indolyl, quinolyl, pyrazolyl, pyrrolyl, pyridinyl, furyl, N-methylbenzotriazolyl, hydroxyethyl, propenyl, (ethoxycarbonyl)propyl, or tetrahydropyranyloxybutyl,

wherein R 1 has

(a) 0-3 substituents independently selected from cyano, methyl, methoxy, pyrazolyl, furyl, hydroxyethyl, acetamido, pyrrolyl, and propenyl, and

(b) 0-1 substituents selected from benzotriazolyl, N-methyl-benzotriazolyl, and benzo[d][1,3]dioxolyl,

T is C═O, —CH 2 —, —CH 2 —CH 2 —, —CH═CH— (cis or trans), propenylene, —CH═CH—CH 2 — (cis or trans), —CH 2 —CH═CH— (cis or trans), ethynylene, or vinylene;

R 2 is selected from phenyl, phenoxy, benzyloxy, naphthyl, furyl, isoquinolinyl, quinolyl, indolyl, pyrazolyl, thiazolyl, anthryl, and benzothienyl,

wherein R 2 is substituted with 0 to 2 substituents,

(a) wherein between 0 and 2 substituents are independently selected from methyl, methoxy, trifluoromethoxy, hydroxyl, hydroxymethyl, fluoro, chloro, bromo, dimethylamino, t-butyl, and isobutoxy; and

(b) between 0 and 1 substituents are selected from phenyl, pyridyl, pyrazolyl, furyl, benzoyl, pyrrolyl, pyridinyl, naphthyl, phenoxy, benzo[d][1,3]dioxolyl, cyclohexyl, cyclopentyl, cyclobutyl, and cyclopropyl;

X is methylene, ethylene, or propenylene; and

R 3 is selected from phenyl, biphenylyl, thiophenyl, bithiophenylyl, diphenylmethanyl, triazolyl, thienyl, benzofuryl, phenanthryl, anthryl, fluorenyl, acenaphthyl, pyrenyl, indanyl, adamantyl, carbazolyl, N-methylcarbazolyl, indolyl, pyrrolidinyl, quinolyl, pyrrolyl, naphthyl, methylnaphthyl, methoxynaphthyl, dimethylthienyl, benzothiadiazolyl, benzimidazolyl, benzothienyl, benzodioxanyl, benzodioxepinyl, benzodioxocinyl, and benzo[d][1,3]dioxolyl,

wherein R 3 is substituted with 0 to 4 substituents independently selected from methyl, trifluoromethyl, methoxy, trifluoromethoxy, chloro, fluoro, bromo, ethenyl, ethoxy, ethyl, isopropyl, t-butyl, propyloxy, amino, dimethylamino, methylamino, allyloxy, (methyl)(phenyl)amino, methanesulfonyl, t-butoxycarbonylmethylamino, t-butoxycarbonyl, boronic acid moiety, and methylcarbonylamin;

and wherein either R 1 is C 1-6 alkoxy or X is propenylene;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein R 1 is hydroxymethyl, methoxy, methoxymethyl, methylthio, phenyl, indolyl, pyrazolyl, pyrrolyl, pyridinyl, furyl, N-methylbenzotriazolyl, or hydroxyethyl; and wherein R 1 has 0 to 2 substituents.

3. The compound of claim 1 , wherein R 2 is selected from phenyl, naphthyl, furyl, isoquinolinyl, quinolyl, indolyl, pyrazolyl, thiazolyl, and benzothienyl, wherein R 2 is substituted with 0 to 2 groups, wherein between 0 and 2 substituents are independently selected from methyl, methoxy, trifluoromethoxy, hydroxyl, fluoro, and hydroxymethyl.

4. The compound of claim 1 , wherein X is methylene.

5. The compound of claim 1 , wherein T is —CH 2 —, —CH═CH— (cis or trans), —CH═CH—CH 2 — (cis or trans), —CH 2 —CH═CH— (cis or trans), ethynylene, or vinylene.

6. The compound of claim 4 , wherein T is methylene, —CH═CH—CH 2 -(trans), or —CH 2 —CH═CH— (trans).

7. The compound of claim 1 , wherein Q is methylene.

8. The compound of claim 1 , wherein Q is ethylene.

9. The compound of claim 1 , wherein:

R 3 is selected from the group consisting of phenyl, biphenylyl, thiophenyl, bithiophenylyl, triazolyl, thienyl, benzofuryl, phenanthryl, indolyl, pyrrolidinyl, quinolyl, pyrrolyl, naphthyl, methylnaphthyl, methoxynaphthyl, dimethylthienyl, benzothiadiazolyl, benzimidazolyl, benzothiophenyl, benzodioxanyl, benzodioxepinyl, benzodioxocinyl, and benzo[d][1,3]dioxolyl;

wherein R 3 is substituted with between 0 and 3 substituents independently selected from methyl, trifluoromethyl, methoxy, trifluoromethoxy, chloro, fluoro, bromo, ethenyl, ethoxy, ethyl, isopropyl, t-butyl, propyloxy, amino, dimethylamino, methylamino, allyloxy, (methyl)(phenyl)amino, methanesulfonyl, t-butoxycarbonylmethylamino, t-butoxycarbonyl, boronic acid moiety, and methylcarbonylamino.

10. The compound of claim 7 , wherein R 3 is phenyl, naphthyl, anthryl, biphenylyl, fluorenyl, or acenapthyl with between 0 and 3 substituents independently selected from fluoro, bromo methyl, methoxy, and hydroxymethyl.

11. The compound of claim 1 , wherein R 1 is methoxymethyl or hydroxymethyl.

12. The compound of claim 1 , wherein R 1 is C 1-4 hydroxyalkyl, (C 1-3 alkoxy)C 1-3 alkyl, C 1-3 alkylthio, C 2-5 alkenyl, hydroxyethyl, propenyl, or (ethoxycarbonyl)propyl; wherein R 1 has 0-3 substituents independently selected from cyano, methyl, methoxy, hydroxyethyl, acetamido, and propenyl.

13. The compound of claim 1 , wherein R 2 is a phenyl group with between 0 and 3 substituents independently selected from methoxy, trifluoromethoxy, fluoro, and methyl.

14. The compound of claim 1 , wherein:

R 1 is hydroxymethyl, methoxy, methoxymethyl, methylthio, phenyl, pyrazolyl, pyrrolyl, pyridinyl, furyl, or N-methylbenzotriazolyl; or R 1 is phenyl independently substituted with methyl, methoxy, pyrazolyl, furyl, benzotriazolyl, N-methyl-benzotriazolyl, or pyrrolyl;

T is —CH 2 —, —CH 2 —CH 2 —, —CH═CH—CH 2 — (trans), ethynylene, or allyl;

R 2 is selected from phenyl, naphthyl, furyl, quinolyl, indolyl, pyrazolyl, thiazolyl, and benzothienyl, wherein R 2 is substituted with 0-2 groups, wherein between 0 and 2 substituents are independently selected from methyl, methoxy, trifluoromethoxy, hydroxyl, and hydroxymethyl; and

R 3 is selected from phenyl, naphthyl, thienyl, benzofuryl, indolyl, isoquinolinyl, quinolyl, pyridinyl, pyrrolyl, benzothiadiazolyl, and benzimidazolyl,

wherein R 3 is substituted with between 0 and 2 substituents-independently selected from methyl, trifluoromethyl, methoxy, trifluoromethoxy, chloro, fluoro, bromo, ethenyl, ethoxy, ethyl, dimethylamino, and methylamino.

15. The compound of claim 1 , wherein:

R 1 is hydroxymethyl, methoxy, methoxymethyl, methylthio, phenyl, pyrazolyl, pyrrolyl, pyridinyl, furyl, C 1-8 hydroxyalkyl, or N-methylbenzotriazolyl;

or R 1 is substituted with 0 to I substituents selected from methyl, methoxy, pyrazolyl, furyl, pyridinyl, benzotriazolyl, N-methyl-benzotriazolyl, and pyrrolyl;

T is —CH 2 —, —CH 2 —CH 2 —, —CH═CH—CH 2 — (trans), ethynylene, or allyl;

R 2 is selected from phenyl, naphthyl, furyl, quinolyl, indolyl, pyrazolyl, benzo[d][1,3]dioxolyl, thiazolyl, and benzothienyl,

wherein R 7 is substituted with 0-3 groups, wherein between 0 and 3 substituents are independently selected from methyl, methoxy, trifluoromethoxy, hydroxyl, and hydroxymethyl;

X is methylene;

R 3 is selected from phenyl, naphthyl, thienyl, benzofuryl, indolyl, pyrrolidinyl, isoquinolyl, quinolyl, pyrrolyl, benzothiadiazolyl, benzimidazolyl, and benzothiophenyl;

wherein R 7 is substituted with between 0 and 2 substituents independently selected from methyl, trifluoromethyl, methoxy, trifluoromethoxy, chloro, fluoro, bromo, ethenyl, ethoxy, ethyl, dimethylamino, and methylamino.

16. A compound selected from the group consisting of:

ER #

Structure

ER 818561

ER 817135

ER 813508

ER 813509

ER 813493

ER 813510

ER 813511

ER 817118

ER 817137

ER 817119

ER 818573

ER 818567

ER 818550

ER 813512

and pharmaceutically acceptable salts thereof.

17. A compound selected from the group consisting of:

ER #

Structure

ER 813081

ER 813077

ER 818528

ER 818574

ER 813411

ER 813078

ER 813521

ER 817116

ER 813080

ER 813519

ER 813492

ER 813452

ER 813410

ER 812605

and pharmaceutically acceptable salts thereof.

18. A compound selected from the group consisting of:

ER #

Structure

ER 818568

ER 813091

ER 813075

ER 818562

ER 813096

ER 819695

ER 813092

ER 813082

ER 820087

ER 813079

ER 813089

ER 813529

ER 813414

ER 813516

and pharmaceutically acceptable salts thereof.

19. A compound selected from the group consisting of:

ER #

Structure

ER 818558

ER 818559

ER 818560

ER 818554

ER 818535

ER 818564

ER 818524

ER 817117

and pharmaceutically acceptable salts thereof.

20. A compound of formula II:

wherein:

Q is a straight or branched, saturated or unsaturated C 1-6 alkylene chain;

R 1 is an substituted phenyl ring or an optionally substituted 6-membered heteroaryl ring having 1-2 nitrogens;

T is a straight or branched, saturated or unsaturated C 1-6 alkylene chain;

R 2 is an optionally substituted phenyl or naphthyl ring, or an optionally substituted 5-membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

X is methylene, ethylene, or propenylene; and

R 3 is phenyl or naphthyl; wherein R 3 is optionally substituted with pyrrolidinyl, morpholinyl, piperidinyl, furyl, thienyl, phenyl, —N(Me)phenyl, dimethylamino, methoxy, ethoxy, methyl, t-butyl, pyridyl, -methylamino, —C(═O)OMe, C(═O)OCH 2 phenyl, amino, hydroxyl, hydroxyethoxy, trifluoromethoxy, trifluoromethyl, or —SO 2 phenyl;

or a pharmaceutically acceptable salt, thereof.

21. A compound of formula III:

wherein:

Q is —CH 2 O—, (CH 2 ) 2 O—, —(CH 2 ) 3 O—, (CH 2 ) 4 O—, —(CH 2 ) 6 O—, —CH 2 OCH 2 —, —(CH 2 ) 2 OCH 2 —, —(CH 2 ) 3 OCH 2 —, —(CH 2 ) 4 OCH 2 —, —(CH 2 ) 6 OCH 2 —, —(CH 2 ) 2 S—, —CH 2 —, —(CH 2 ) 2 —, —(CH 2 ) 3 —, —(CH 2 ) 4 —, —CH 2 CH═CH—, —CH 2 C(═CH 2 )CH 2 —, —CH 2 CH 2 CH═CH—, —CH 2 CH(CH 3 )CH 2 —, —CH 2 C(═O)OCH 2 —, CH 2 CH═C(CH 3 )CH 2 CH 2 CH═C(CH 3 )—, —CH 2 C—CCH 2 CH 2 —, —CH 2 C(═O)CH 2 —, (CH 2 ) 4 C(═O)OCH 2 CH 2 —, —(CH 2 ) 5 C(═O)OCH 2 CH 2 —, —(CH 2 ) 6 C(═O)OCH 2 CH 2 —CH 2 C(═O)N(Et)CH 2 CH 2 —, or —CH 2 CH 2 N(CH 3 )CH 2 —;

R 1 is CN, pyridyl, thiazolyl, tetrahydrofuranyl, tetrahydro-2H-pyranyl, phenyl, isoxazolyl, pyrrolyl, benztriazolyl, cyclohexyl, cyclopropyl, or thienyl;

T is —CH 2 O—, —(CH 2 ) 2 O—, —(CH 2 ) 3 O—, —(CH 2 ) 4 O—, —(CH 2 ) 6 O—, —CH 2 OCH 2 —, —(CH 2 ) 2 OCH 2 —, —(CH 2 ) 3 OCH 2 —, —(CH 2 ) 4 OCH 2 —, —(CH 2 ) 6 OCH 2 —, —(CH 2 ) 2 S—, —CH 2 —, —(CH 2 ) 2 —, —(CH 2 ) 3 —, —(CH 2 ) 4 —, —CH 2 CH═CH—, —CH 2 CH═CHCH 2 —, —CH 2 C(═CH 2 )CH 2 —, —CH 2 CH 2 CH═CH—, —CH 2 CH(CH 3 )CH 2 —, —CH 2 C(═O)OCH 2 —, —CH 2 CH═C(CH 3 )CH 2 CH 2 CH═C(CH 3 )—, —CH 2 C≡C— or —CH 2 C≡CCH 2 CH 2 —;

R 2 is optionally substituted phenyl, naphthyl, quinolinyl, phthalimidyl, isoquinolinyl, indolyl, thienyl, furyl, isoxazolyl, or thiazolyl;

X is —CH 2 —, —CH 2 CH 2 —, or —CH 2 CH═CH—; and

R 3 is phenyl or naphthyl; wherein R 3 is optionally substituted with pyrrolidinyl, morpholinyl, piperidinyl, furyl, thienyl, phenyl, —N(Me)phenyl, dimethylamino, methoxy, ethoxy, methyl, t-butyl, pyridyl, methylamino, —C(═O)OMe, —C(═O)OCH 2 phenyl, amino, hydroxyl, hydroxyethoxy, trifluoromethoxy, trifluoromethyl, or —SO 2 phenyl;

or a pharmaceutically acceptable salt, thereof.

22. A compound of formula IV:

wherein:

Q is —CH 2 O—, —(CH 2 ) 2 O—, —(CH 2 ) 3 O—, —(CH 2 ) 4 O—, —(CH 2 ) 6 O—, —CH 2 OCH 2 —, —(CH 2 ) 2 OCH 2 —, —(CH 2 ) 3 OCH 2 —, —(CH 2 ) 4 OCH 2 —, —(CH 2 ) 6 OCH 2 —, or

R 1 is hydrogen;

T is —CH 2 —, —(CH 2 ) 2 —, —(CH 2 ) 3 —, —(CH 2 ) 4 —, —CH 2 CH═CH—, —CH 2 CH═CHCH 2 —, —CH 2 C(═CH 2 )CH 2 —, —CH 2 CH 2 CH═CH—, —CH 2 CH(CH 3 )CH 2 —, —CH 2 C(═O)OCH 2 —, —CH 2 CH═C(CH 3 )CH 2 CH 2 CH═C(CH 3 )—, —CH 2 C≡C— or CH 2 C═CCH 2 CH 2 —;

R 2 is optionally substituted phenyl or naphthyl;

X is —CH 2 —; and

R 3 is a phenyl or naphthyl ring; wherein R 3 is optionally substituted with pyrrolidinyl, morpholinyl, piperidinyl, furyl, thienyl, phenyl, —N(Me)phenyl, dimethylamino, methoxy, ethoxy, methyl, t-butyl, pyridyl, —NHMe, —C(═O)OMe, —C(═O)OCH 2 phenyl, amino, hydroxyl, hydroxyethoxy, trifluoromethoxy, trifluoromethyl, or —SO 2 phenyl;

or a pharmaceutically acceptable salt thereof.

23. A pharmaceutical composition comprising a compound of claim 1 , 14 , 15 , 16 , 17 , 18 , or 19 .

24. A method for treating rheumatoid arthritis in a patient, comprising the step of administering to a patient in need of treatment a pharmaceutical composition comprising a compound of claim 1 .

25. A method for treating multiple sclerosis in a patient, comprising the step of administering to a patient in need of treatment a pharmaceutical composition comprising a compound of claim 1 .

26. A method for treating an autoimmune disease, comprising the step of administering to a patient in need of treatment a pharmaceutical composition comprising a compound of claim 1 .

27. The method of claim 26 , wherein said autoimmune disease is selected from the group consisting of Crohn's disease, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, type I diabetes mellitus, HTLV-1-associated myelopathy/tropical spastic paraparesis, artherosclerosis, Hodgkin's Lymphoma, B-cell lymphoblastic leukemia/lymphoblastic lymphoma, chronic lymphocytic leukemia, marginal zone lymphoma, and hairy cell leukemia, Behcet's disease, Coeliac disease, and T-cell-mediated liver inflammation.

28. The method of claim 26 , wherein said autoimmune disease is inflammatory bowel disease.

29. The compound of claim 1 , wherein R 1 is C 1-6 alkoxy.

30. The compound of claim 1 , wherein X is propenylene.