Phenyl carboxamide compounds useful as beta-secretase inhibitors for the treatment of alzheimer's disease

1. A compound of formula (I):

wherein

R 1 is selected from the group consisting of:

wherein R 1a and R 1b are selected from the group consisting of

(a) hydrogen,

(b) halogen,

(c) phenyl,

(d) —CN,

(e) —C(═O)—R 1c , wherein R 1c is hydrogen or C 1-10 alkyl,

(f) —C 3-12 cycloalkyl, and

(g) —X—R 1d ,

wherein X is selected from the group consisting of

(i) —O—,

(ii) —C(═O)—,

(iii) —S—,

(iv) —S(═O)—, and

(v) —S(═O) 2 —,

and R 1d is selected from the group consisting of

(i) —C 1-6 alkyl,

(ii) —C 1-3 alkoxy,

(iii) —C 3-12 cycloalkyl, and

(iv) phenyl;

or R 1a and R 1b are linked together to form the group —O—CH 2 CH 2 —O— or —CH═CH—CH═CH—;

or R 1 is selected from the group consisting of

(2) —C(═O)NR 1e R 1f ,

(3) —OSO 2 R 1g , and

(4) —N(R 1g )SO 2 R 1h ;

wherein R 1e , R 1f , R 1g and R 1h are independently selected from the group consisting of

(a) —C 1-6 alkyl,

(b) —C 2-6 alkenyl,

(c) —C 2-6 alkynyl,

(d) —C 0-6 alkyl-C 3-12 cycloalkyl,

(e) —C 1-6 alkyl-di(C 3-12 cycloalkyl),

(f) —C 0-6 alkyl-aryl,

(g) —C 0-6 alkenyl-aryl,

(h) —C 0-6 alkyl-di(aryl), and

(i) —C 0-6 alkyl-heteroaryl;

wherein said heteroaryl is selected from the group consisting of pyrazinyl, pyrazolyl,

pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, tetrazolyl, furanyl, imidazolyl, triazinyl, pyranyl, thiazolyl, thienyl, thiophenyl, triazolyl, oxazolyl, isoxazolyl, thiazolyl, oxadiazolyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl and benzoxazolyl,

and said aryl is selected from the group consisting of phenyl and naphthyl,

and said alkyl, alkenyl, cycloalkyl, aryl and heteroaryl are unsubstituted or substituted with one or more

(i) halo,

(ii) —OH,

(iii) ═O,

(iv) —CN,

(v) —CF 3 ,

(vi) —OCF 3 ,

(vii) —C 1-6 alkyl,

(viii) —C 1-3 alkoxy,

(ix) —C 3-12 cycloalkyl,

(x) phenyl,

(xi) —N 3 , or

(xii) —X—R 1d ,

or R 1e and R 1f are linked with the nitrogen atom to which they are attached to form a 5-7 membered heterocyclic ring,

R 2 is selected from the group consisting of

(1) hydrogen, and

(2) —C 1-6 alkyl; and

R 3a , R 3b and R 3c are independently selected from the group consisting of

(1) hydrogen,

(2) halo,

(3) —OH,

(4) —CN,

(5) —CF 3 ,

(6) —OCF 3

(7) —C 1-6 alkyl,

(8) —C 1-3 alkoxy,

(9) —C 3-12 cycloalkyl, and

(10) —NHC(═O)CH 2 NR 1a R 1b ;

and pharmaceutically acceptable salts thereof, and individual enantiomers and diastereomers thereof.

2. The compound of claim 1 wherein R 2 is —C 1-6 alkyl.

3. The compound of claim 2 wherein R 2 is methyl.

4. The compound of claim 1 wherein R 6a and R 6c are hydrogen, and R 6b is selected from the group consisting of hydrogen and halogen.

5. The compound of claim 4 wherein R 6b is halogen.

6. The compound of claim 5 wherein R 6b is fluoro.

7. The compound of claim 1 wherein R 1 is aryl.

8. The compound of claim 7 wherein R 1 is phenyl, which is unsubstituted or substituted with cyano.

9. The compound of claim 1 wherein R 1 is selected from the group consisting of

(1) —C(═O)NR 1e R 1f ,

(2) —OSO 2 R 1g , and

(3) —N(R 1g )SO 2 R 1h .

10. The compound of claim 9 wherein R 1 is —OSO 2 R 1g .

11. The compound of claim 10 wherein R 1g is phenyl.

12. A compound of claim 1 which is selected from the group consisting of

and pharmaceutically acceptable salts thereof.

13. The compound of claim 12 which is

or a pharmaceutically acceptable salt thereof.

14. The pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.