Pyrido[2,3-B] pyrazin-3(4H)-ones for use as stearoyl CoA desaturase inhibitors

1. A compound having the structure of Formula I:

wherein

R 1 is

a) 4 to 6 membered optionally substituted nitrogen containing monocyclic heterocycle,

wherein the heterocycle moiety optionally substituted with from 1 to 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, keto, oxo, thiocarbonyl, carboxy, carboxyalkyl, arylthio, heteroarylthio, heterocyclylthio, thiol, alkylthio, aryl, aryloxy, heteroaryl, aminosulfonyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, —SO-alkyl, —SO-aryl, —SO-heteroaryl, —SO 2 —alkyl, SO 3 -aryl and —SO 2 -heteroaryl, and

further wherein each optional alkyl, heteroaryl, aryl, and heterocyclyl substituent is further optionally substituted with halo, NO 2 , alkyl, CF 3 , amino, mono- or di-alkylamino, alkyl or aryl or heteroaryl amide, NR 20 COR 22 , NR 20 SO 2 R 22 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , NR 20 CON(R 20 ) 2 , OC(O)R 20 , OC(O)N(R 20 ) 2 , S(O) 3 R 20 , P(O)(OR 20 ) 2 , SR 20 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , CN, or OR 20 ;

b) —X—NR 4 R 5 ,

c) —X—C(O)NR 4 R 5 ,

d) —X—C(O)OR 7 , or

e) —X—OR 7

wherein

R 4 is hydrogen or C 1-4 lower alkyl, and

R 5 is hydrogen, C 1-4 lower alkyl, aryl, heteroaryl, —C 1-4 alkoxy, C(═NH)NH 2 , —C(═O)R 6 or —S(═O) 2 R 6 , wherein

R 6 is hydrogen, optionally substituted C 1-4 alkyl, optionally substituted C 1-4 alkenyl, C 1-4 alkoxy, 5 or 6 membered optionally substituted monocyclic aryl, or 5 or 6 membered optionally substituted monocyclic heteroaryl, or

R 4 and R 5 along with the nitrogen to which they are attached join to form a 5 or 6 membered monocyclic heteroaryl or heteroalkyl ring;

R 7 is hydrogen, optionally substituted C 1-4 alkyl, optionally substituted C 1-4 alkenyl, 5 or 6 membered optionally substituted monocyclic aryl, or 5 or 6 membered optionally substituted monocyclic heteroaryl,

X is C 2-4 linear or branched alkylene;

wherein each R 6 and R 7 alkyl, alkenyl, aryl or heteroaryl moiety is optionally substituted with from 1 to 3 substituents independently selected from the group consisting of alkyl, heterocyclyl, aryl, heteroaryl, halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , S(O) 3 R 20 , P(O)(OR 20 ) 2 , SO 2 NR 20 COR 22 , SO 2 NR 20 CO 2 R 22 , SO 2 NR 20 CON(R 20 ) 2 , NR 20 COR 22 , NR 20 CO 2 R 22 , NR 20 CON(R 20 ) 2 , NR 20 C(NR 20 )NHR 23 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , CONR 20 SO 2 R 22 , NR 20 SO 2 R 22 , SO 2 NR 20 CO 2 R 22 , OCONR 20 SO 2 R 22 , OC(O)R 20 , C(O)OCH 2 OC(O)R 20 , and OCON(R 20 ) 2 , and

further wherein each optional alkyl, heteroaryl, aryl, and heterocyclyl substituent is further optionally substituted with halo, NO 2 , alkyl, CF 3 , amino, mono- or di-alkylamino, alkyl or aryl or heteroaryl amide, NR 20 COR 22 , NR 20 SO 2 R 22 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , NR 20 CON(R 20 ) 2 , OC(O)R 20 , OC(O)N(R 20 ) 2 , S(O) 3 R 20 , P(O)(OR 20 ) 2 , SR 20 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , CN, or OR 20 ;

R 2 is optionally substituted aryl, or heteroaryl;

wherein the aryl or heteroaryl moiety is optionally substituted with from 1 to 3 substituents independently selected from the group consisting of alkyl, heterocyclyl, aryl, heteroaryl, halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , S(O) 3 R 20 , P(O)(OR 20 ) 2 , SO 2 NR 20 COR 22 , SO 2 NR 20 CO 2 R 22 , SO 2 NR 20 CON(R 20 ) 2 , NR 20 COR 22 , NR 20 CO 2 R 22 , NR 20 CON(R 20 ) 2 , NR 20 C(NR 20 )NHR 23 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , CONR 20 SO 2 R 22 , NR 20 SO 2 R 22 , SO 2 NR 20 CO 2 R 22 , OCONR 20 SO 2 R 22 , OC(O)R 20 , C(O)OCH 2 OC(O)R 20 , and OCON(R 20 ) 2 , and

further wherein each optional alkyl, heteroaryl, aryl, and heterocyclyl substituent is further optionally substituted with halo, NO 2 , alkyl, CF 3 , amino, mono- or di-alkylamino, alkyl or aryl or heteroaryl amide, NR 20 COR 22 , NR 20 SO 2 R 22 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , NR 20 CON(R 20 ) 2 , OC(O)R 20 , OC(O)N(R 20 ) 2 , S(O) 3 R 20 , P(O)(OR 20 ) 2 , SR 20 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , CN, or OR 20 ;

R 3 is hydrogen, optionally substituted C 1-4 alkyl, 6 membered optionally substituted monocyclic aryl, or 5 or 6 membered optionally substituted monocyclic heteroaryl;

wherein the alkyl, aryl, or heteroaryl moiety is optionally substituted with from 1 to 3 substituents independently selected from the group consisting of alkyl, heterocyclyl, aryl, heteroaryl, halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , S(O) 3 R 20 , P(O)(OR 20 ) 2 , SO 2 NR 20 COR 22 , SO 2 NR 20 CO 2 R 22 , SO 2 NR 20 CON(R 20 ) 2 , NR 20 COR 22 , NR 20 CO 2 R 22 , NR 20 CON(R 20 ) 2 , NR 20 C(NR 20 )NHR 23 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , CONR 20 SO 2 R 22 , NR 20 SO 2 R 22 , SO 2 NR 20 CO 2 R 22 , OCONR 20 SO 2 R 22 , OC(O)R 20 , C(O)OCH 2 OC(O)R 20 , and OCON(R 20 ) 2 , and

further wherein each optional alkyl, heteroaryl, aryl, and heterocyclyl substituent is further optionally substituted with halo, NO 2 , alkyl, CF 3 , amino, mono- or di-alkylamino, alkyl or aryl or heteroaryl amide, NR 20 COR 22 , NR 20 SO 2 R 22 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , NR 20 CON(R 20 ) 2 , OC(O)R 20 , OC(O)N(R 20 ) 2 , S(O) 3 R 20 , P(O)(OR 20 ) 2 , SR 20 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , CN, or OR 20 ;

R 20 and R 22 are independently selected from the group consisting of hydrogen, C 1-15 alkyl, C 2-15 alkenyl, C 2-15 alkynyl, heterocyclyl, aryl, and heteroaryl,

wherein the alkyl, alkenyl, alkynyl, heterocyclyl, aryl, and heteroaryl moieties are optionally substituted with from 1 to 3 substituents independently selected from halo, alkyl, mono- or dialkylamino, alkyl or aryl or heteroaryl amide, CN, O—C 1-6 alkyl, CF 3 , aryl, and heteroaryl;

Q is C 1-4 alkylene which may optionally contain one or more —NH—, —O—, —S—, or carbonyl linking moieties;

W 1 is CH; and

W 2 is N;

or a pharmaceutically acceptable salt or ester, thereof.

2. The compound of claim 1 , wherein R 1 is —X—NR 4 R 5 , —X—C(O)NR 4 R 5 , —X—C(O)OR 7 , or —X—OR 7 and R 2 is optionally substituted 6-membered monocyclic aryl or optionally substituted 5- or 6-membered heteroaryl.

3. The compound of claim 1 , wherein R 1 is —X—NR 4 R 5 and R 3 is 6 membered optionally substituted monocyclic aryl.

4. The compound of claim 3 , selected from the group consisting of:

N-[2-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

N-[2-(6-{[(4-fluorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

N-[2-(6-{[(3-chlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

N-[2-(6-{[(3-chloro-4-fluorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

N-{2-[2-(4-methoxyphenyl)-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-{2-[2-(4-methoxyphenyl)-3-oxo-6-({[4-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-[2-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methylthiophenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

N-[2-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methylphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

N-[2-(6-{[(3-bromophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

N-{2-[6-({[3,5-bis(trifluoromethyl)phenyl]methyl}amino)-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-{2-[6-({[4-fluoro-3-(trifluoromethyl)phenyl]methyl}amino)-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-{2-[2-(4-methoxyphenyl)-3-oxo-6-({[5-(trifluoromethyl)(3-pyridyl)]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-(2-{2-(4-methoxyphenyl)-3-oxo-6-[benzylamino]-4-hydropyridino[2,3-b]pyrazin-4-yl}ethyl)acetamide;

N-(2-{2-(4-methoxyphenyl)-3-oxo-6-[(3-pyridylmethyl)amino]-4-hydropyridino[2,3-b]pyrazin-4-yl}ethyl)acetamide;

N-[2-(6-{[(3-fluorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

4-(2-aminoethyl)-6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-4-hydropyridino[3,2-b]pyrazin-3-one;

N-[2-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo(4-hydropyridino[2,3-b]pyrazin-4-yl))ethyl](tert-butoxy)carboxamide;

N-[2-(6-{[(2-chlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

N-(2-{2-(4-methoxyphenyl)-3-oxo-6-[(3-phenylpropyl)amino]-4-hydropyridino[2,3-b]pyrazin-4-yl}ethyl)acetamide;

N-{2-[2-(4-methoxyphenyl)-3-oxo-6-({[6-(trifluoromethyl)(2-pyridyl)]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-[2-(2-(4-methoxyphenyl)-6-{[(5-methyl(1,2,4-oxadiazol-3-yl))methyl]amino}-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

N-[2-(2-(4-methoxyphenyl)-6-{[(3-methoxyphenyl)methyl]amino}-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

methyl 3-[({4-[2-(acetylamino)ethyl]-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[5,6-b]pyrazin-6-yl}amino)methyl]benzoate;

3-[({4-[2-(acetylamino)ethyl]-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[5,6-b]pyrazin-6-yl}amino)methyl]benzoic acid;

N-[2-(2-(4-methoxyphenyl)-6-{[(3-methylphenyl)methyl]amino}-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

N-{2-[2-(4-methoxyphenyl)-3-oxo-6-({[3-(trifluoromethoxy)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-(2-{2-(4-methoxyphenyl)-3-oxo-6-[(2-pyridylmethyl)amino]-4-hydropyridino[2,3-b]pyrazin-4-yl}ethyl)acetamide;

N-{2-[6-({[2-fluoro-5-(trifluoromethyl)phenyl]methyl}amino)-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-[2-(2-(4-methoxyphenyl)-6-{[(5-methylisoxazol-3-yl)methyl]amino}-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

N-{2-[2-[4-(2-methoxyethoxy)phenyl]-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-{2-[3-oxo-2-(4-propylphenyl)-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-{2-[2-[4-(acetylamino)phenyl]-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-{2-[2-(4-methylphenyl)-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-{2-[2-(4-ethylphenyl)-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-{2-[2-(4-fluorophenyl)-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-[2-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo(4-hydropyridino[2,3-b]pyrazin-4-yl))ethyl]-2-(dimethylamino)acetamide;

{N-[2-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]carbamoyl}methyl acetate;

N-[2-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo(4-hydropyridino[2,3-b]pyrazin-4-yl))ethyl]-2-hydroxyacetamide;

2-amino-N-[2-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo(4-hydropyridino[2,3-b]pyrazin-4-yl))ethyl]acetamide

2-(acetylamino)-N-[2-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo(4-hydropyridino[2,3-b]pyrazin-4-yl))ethyl]acetamide;

N-[2-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-[4-(methylsulfonyl)phenyl]-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

N-[2-(2-(3,4-dichlorophenyl)-6-{[(3,4-dichlorophenyl)methyl]amino}-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

N-[2-(6-{[3-(2,5-dichlorophenoxy)propyl]amino}-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

{N-[2-(4-methoxyphenyl)-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]carbamoyl}methyl acetate; and

N-{2-[3-oxo-2-[4-(trifluoromethyl)phenyl]-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide.

5. The compound of claim 2 , wherein R 1 is —X—NR 4 R 5 and R 3 is 5- or 6-membered optionally substituted monocyclic heteroaryl.

6. The compound of claim 5 , selected from the group consisting of:

N-[2-(6-{[(3,4-dichlorophenyl)methyl]amino}-3-oxo-2-(3-pyridyl)-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

N-[2-(6-{[(3-chloro-4-fluorophenyl)methyl]amino}-3-oxo-2-(3-pyridyl)-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide; and

N-{2-[3-oxo-2-(3-pyridyl)-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide.

7. The compound of claim 2 , wherein R 1 is —X—NR 4 R 5 and R 3 is hydrogen.

8. The compound of claim 7 , selected from the group consisting of:

N-{2-[3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide; and

N-[2-(6-{[(3,4-dichlorophenyl)methyl]amino}-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide.

9. The compound of claim 2 , wherein R 3 is optionally substituted C 1-4 alkyl.

10. The compound of claim 9 , selected from the group consisting of:

N-{2-[3-oxo-2-(trifluoromethyl)-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-{2-[2-methyl-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-[2-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-methyl-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)ethyl]acetamide;

N-{2-[3-oxo-2-propyl-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-{2-[2-ethyl-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

N-{2-[3-oxo-2-(2-phenylethyl)-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]ethyl}acetamide;

4-[2-methyl-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]butanamide.

11. The compound of claim 1 , wherein R 1 is —X—C(O)NR 4 R 5 and R 3 is 6-membered optionally substituted monocyclic aryl.

12. The compound of claim 11 , selected from the group consisting of:

3-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)propanamide;

3-[2-(4-methoxyphenyl)-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]propanamide;

4-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo(4-hydropyridino[2,3-b]pyrazin-4-yl))-N-methylbutanamide;

4-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)butanamide;

3-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo(4-hydropyridino[2,3-b]pyrazin-4-yl))-N-methylpropanamide;

3-[2-(4-methoxyphenyl)-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino) (4-hydropyridino[2,3-b]pyrazin-4-yl)]-N-(phenylmethoxy)propanamide;

N-methoxy-3-[2-(4-methoxyphenyl)-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)(4-hydropyridino[2,3-b]pyrazin-4-yl)]propanamide;

3-[2-(4-methoxyphenyl)-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)(4-hydropyridino[2,3-b]pyrazin-4-yl)]-N-methylpropanamide;

(3R)-3-[2-(4-methoxyphenyl)-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)(4-hydropyridino[2,3-b]pyrazin-4-yl)]butanamide;

3-[2-(4-methylphenyl)-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]propanamide;

3-[2-(4-ethylphenyl)-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]propanamide;

3-[2-[4-(2-methoxyethoxy)phenyl]-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]propanamide;

3-[3-oxo-2-(4-propylphenyl)-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]propanamide;

4-[2-(4-methoxyphenyl)-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]butanamide;

3-[3-oxo-2-[4-(trifluoromethyl)phenyl]-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]propanamide;

2-[2-(4-methoxyphenyl)-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]acetamide;

(3S)-3-[2-(4-methoxyphenyl)-3-oxo-6-({[3-(trifluoromethyl)phenyl]methyl}amino)(4-hydropyridino[2,3-b]pyrazin-4-yl)]butanamide; and

3-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo(4-hydropyridino[2,3-b]pyrazin-4-yl))-N-(2-hydroxyethyl)propanamide.

13. The compound of claim 1 , wherein R 1 is —X—C(O)NR 4 R 5 and R 3 is 5 or 6 membered optionally substituted monocyclic heteroaryl.

14. The compound of claim 13 , selected from the group consisting of:

3-(6-{[(3,4-dichlorophenyl)methyl]amino}-3-oxo-2-(3-pyridyl)-4-hydropyridino[2,3-b]pyrazin-4-yl)propanamide; and

3-[3-oxo-2-(3-pyridyl)-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[2,3-b]pyrazin-4-yl]propanamide.

15. The compound of claim 2 , wherein R 1 is —X—C(O)OR 7 and R 3 is 6 membered optionally substituted monocyclic aryl.

16. The compound of claim 15 , selected from the group consisting of:

ethyl 3-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)propanoate;

ethyl 4-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)butanoate;

4-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)butanoic acid; and

3-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo-4-hydropyridino[2,3-b]pyrazin-4-yl)propanoic acid.

17. The compound of claim 2 , wherein R 1 is —X—OR 7 .

18. The compound of claim 17 , namely 4-(2-hydroxyethyl)-2-(4-methoxyphenyl)-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[3,2-b]pyrazin-3-one.

19. The compound of claim 1 wherein R 1 is a 4- to 6-membered nitrogen containing optionally substituted monocyclic heterocycle.

20. The compound of claim 19 , selected from the group consisting of:

4-((3R)pyrrolidin-3-yl)-6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-4-hydropyridino[3,2-b]pyrazin-3-one;

(3R)-3-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo(4-hydropyridino[2,3-b]pyrazin-4-yl))pyrrolidinecarbaldehyde;

(3S)-3-(6-{[(3,4-dichlorophenyl)methyl]amino}-2-(4-methoxyphenyl)-3-oxo(4-hydropyridino[2,3-b]pyrazin-4-yl))pyrrolidinecarbaldehyde; and

4-((3S)-6-oxo(3-piperidyl))-2-(4-methoxyphenyl)-6-({[3-(trifluoromethyl)phenyl]methyl}amino)-4-hydropyridino[3,2-b]pyrazin-3-one.

21. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt or ester thereof.