Bicyclic pyridinones

1. A compound having the structure of Formula I:

wherein:

X is a 5- to 14-membered heteroaryl containing 1-3 heteroatoms;

R 1 is hydrogen, halogen, C 1-6 alkyl; wherein said alkyl may be optionally and independently substituted with one to three of fluoro, cyano, —CF 3 , hydroxy, or C 1-6 alkoxy;

R 2a and R 2b for each occurrence are each independently hydrogen, fluoro, cyano, —CF 3 , or C 1-6 alkyl; wherein said alkyl, may be optionally and independently substituted with cyano, C 1-3 alkyl or one to three fluoro; or R 2a and R 2b together with the carbon to which they are bonded form a 3- to 5-membered cycloalkyl optionally substituted with one to three R 8 ;

R 3 is ) —(C(R 11 ) 2 ) t -(5- to 14-membered heteroaryl); wherein said heteroaryl moiety may be optionally independently substituted with one to five R 10 ;

R 4a and R 4b are each independently hydrogen, —CF 3 , or C 1-6 alkyl, wherein said alkyl is optionally substituted with one to three —CF 3 , cyano or fluoro;

R 5a and R 5b for each occurrence are each independently hydrogen, —CF 3 , or C 1-6 alkyl, wherein said alkyl is optionally substituted with one to three —CF 3 , cyano or fluoro;

R 6 , R 7 and R 8 are each independently hydrogen, —CF 3 , cyano, halogen, C 1-6 alkyl or —OR 9 ; provided that R 6 and R 7 cannot both be —OH;

R 9 is hydrogen or, C 1-6 alkyl; wherein said alkyl may be optionally and independently substituted with cyano, or one to three fluoro;

each R 10 is independently hydrogen, halogen, cyano, —CF 3 , C 1-6 alkyl —(C(R 11 ) 2 ) m —OR 12 , —C(O)R 13 , —SF 5 or —Si(CH 3 ) 3 ; wherein said alkyl, moieties may be optionally and independently substituted with one to three R 14 ;

each R 11 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-4 cycloalkyl, fluoro, —CF 3 , —CHF 2 or —OR 12 ; wherein said alkyl, alkenyl, alkynyl or cycloalkyl moieties may be optionally independently substituted with one to three fluoro or cyano;

each R 12 is independently hydrogen, C 1-6 alkyl, or —CF 3 ; wherein said alkyl, may be optionally independently substituted with one to three R 16 ;

each R 13 is independently C 1-6 alkyl; wherein said alkyl may be optionally independently substituted with one to three R 16 ;

each R 14 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, cyano, —CF 3 , —CHF 2 , —OR 9 or —OCF 3 ;

R 16 is independently hydrogen, —CF 3 , cyano, halogen, C 1-6 alkyl or —OR 9 ; wherein said alkyl moiety may be optionally substituted with one to three R 17 ;

R 17 is independently hydrogen, hydroxyl, —CF 3 , cyano, fluoro, C 2-6 alkenyl or C 2-6 alkynyl; wherein said alkenyl or alkynyl moiety may be optionally substituted with one to three hydrogen, fluoro or C 1-6 alkyl; and

each t or, m, is an integer independently selected from 0, 1, 2, 3 and 4;

z is an integer selected from 1 and 2;

y is an integer selected from 1, 2, 3 and 4;

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 wherein X is imidazolyl, pyrazolyl, isothiazolyl, thiazolyl, isoxazolyl, oxazolyl or pyridyl.

3. The compound according to claim 2 wherein X is imidazolyl.

4. The compound according to claim 2 wherein R 1 is C 1-6 alkyl.

5. The compound according to claim 3 wherein R 1 is methyl optionally substituted with one hydroxyl or C 1-6 alkoxy or one to three fluoro; y is two or three and z is 1.

6. The compound according to claim 5 wherein R 10 is independently hydrogen, halogen, cyano, —CF 3 , C 1-6 alkyl, —C(R 11 ) 2 ) m —OR 12 or —C(O)R 13 ; wherein the alkyl may be independently substituted with one to three R 14 .

7. The compound according to claim 6 wherein R 11 is independently hydrogen, C 1-6 alkyl, fluoro, —CF 3 , —CHF 2 or —OR 12 ; and R 12 is hydrogen, C 1-6 alkyl, or —CF 3 .

8. The compound according to claim 7 wherein R 3 is 2,3-dihydro-1H-indene, quinoline, isoquinoline, pyrazole, benzo[b]furan, 2,3-dihydrobenzofuran, 1,2-benzisothiazole, 1,3-benzothiazole, benzofuro[3,2-c]pyridine, pyridine, carbazole, benzo[d]isoxazole, benzocyclobutane, 1,2,3,4-tetrahydronaphthalene, dibenzo[b,d]thiophene, dibenzo[b,d]furan or cinnoline.

9. The compound according to claim 8 wherein R 10 is hydrogen, chloro, fluoro, bromo, cyano, —CF 3 , —OCF 3 , methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, cyclopropyl, cyclobutyl, hydroxy, or methoxy.

10. The compound according to claim 9 wherein R 2a and R 2b are hydrogen or C 1-6 alkyl; t is zero and m is zero; or a pharmaceutically acceptable salt thereof.

11. A compound selected from the group consisting of:

2-(2-{[4-fluoro-2-(trifluoromethyl)-1,3-benzothiazol-7-yl]oxy}ethyl)-7-(4-methyl-1H-imidazol-1-yl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione;

7-(4-methyl-1H-imidazol-1-yl)-2-(2-{[2-(trifluoromethyl)-1,3-benzothiazol-7-yl]oxy}ethyl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione;

2-{2-[(2,2-difluoro-2,3-dihydro-1H-inden-4-yl)oxy]ethyl}-7-(4-methyl-1H-imidazol-1-yl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione;

2-{2-[(2,2-difluoro-1,3-benzodioxol-4-yl)oxy]ethyl}-7-(4-methyl-1H-imidazol-1-yl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione;

or a pharmaceutically acceptable salt of any of the above.

12. A method for treating a mammal having Alzheimer's Disease comprising administering to the mammal a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable vehicle, diluent or carrier.

14. The compound according to claim 1 wherein R 2a and R 2b are hydrogen or C 1-6 alkyl; t is zero and m is zero; or a pharmaceutically acceptable salt thereof.