1,3,5-substituted phenyl derivative compounds useful as beta-secretase inhibitors for the treatment of Alzheimer's disease

1. A compound of formula (I):

wherein:

X is selected from the group consisting of

A is selected from the group consisting of

(1) hydrogen,

(2) —C 1-10 alkyl, and

(3) —C 2-10 alkenyl,

wherein said alkyl or alkenyl is unsubstituted or substituted with one or more

(a) halo,

(b) —C 3-12 cycloalkyl,

(c) —OH,

(d) —CN,

(e) —O—C 1-10 alkyl,

(f) phenyl, or

(g) heteroaryl selected from the group consisting of pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, tetrazolyl, furanyl, imidazolyl, triazinyl, pyranyl, thiazolyl, thiophenyl, triazolyl, oxazolyl, isoxazolyl, thiazolyl, oxadiazolyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzofuranyl, and benzoxazolyl,

and said phenyl and heteroaryl is unsubstituted or substituted with one or more

(i) halo,

(ii) —OH,

(iii) —CN,

(iv) —O—C 1-10 alkyl,

(v) —C 1-10 alkyl, or

(vi) —C 3-12 cycloalkyl;

Y is selected from the group consisting of

(1) —OH, and

(2) —NR h R i ,

wherein R h and R i are selected from the group consisting of

(a) hydrogen,

(b) —C 1-10 alkyl, and

(c) —C 0-6 alkyl-C 6-10 aryl,

or when Y is NR h R i , and R h is hydrogen, then R i and A may be linked together to form the group—CH 2 (CH 2 ) q CH 2 —;

Q 1 is C 0-3 alkyl;

R 1 is aryl selected from the group consisting of phenyl and napthyl,

wherein said aryl is unsubstituted or substituted with one or more

(a) halo,

(b) —C 1-10 alkyl, wherein said alkyl is unsubstituted or substituted with one or more halo,

(c) —OH,

(d) —CN,

(e) —O—C 1-10 alkyl, or

(f) —C 3-12 cycloalkyl;

R 2 is

(R 4 —SO 2 )N(R 7 )—, wherein R 4 is selected from the group consisting of

(a) —C 1-10 alkyl, or

(b) —C 3-12 cycloalkyl,

wherein said alkyl and cycloalkyl is unsubstituted or substituted with one or more

(i) halo,

(ii) —OH,

(iii) —CN,

(iv) —C 1-10 alkyl,

(v) —C 1-10 alkyl,

(v) —C 3-12 cycloalkyl,

(vi) aryl selected from the group consisting of phenyl and napthyl, or

(vii) heteroaryl selected from the group consisting of pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, tetrazolyl, furanyl, imidazolyl, triazinyl, pyranyl, thiazolyl, thiophenyl, triazolyl, oxazolyl, isoxazolyl, thiazolyl, oxadiazolyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzofuranyl, and benzoxazolyl,

and said aryl and heteroaryl is unsubstituted or substituted with one or more

 (A) halo,

 (B) —OH,

 (C) —CN,

 (D) —O—C 1-10 alkyl,

 (E) —C 3-12 cycloalkyl, or

 (F) —C 1-10 alkyl; and

R 7 is selected from the group consisting of

(a) hydrogen,

(b) —C 1-10 alkyl,

(c) aryl selected from the group consisting of phenyl and napthyl, and

(d) heteroaryl selected from the group consisting of pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, tetrazolyl, furanyl, imidazolyl, triazinyl, pyranyl, thiazolyl, thiophenyl, triazolyl, oxazolyl, isoxazolyl, thiazolyl, oxadiazolyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzofuranyl, and benzoxazolyl,

wherein said alkyl, aryl and heteroaryl is unsubstituted or substituted with one or more

(i) halo,

(ii) —OH,

(iii) —CN,

(iv) —O—C 1-10 alkyl,

(v) —C 3-8 cycloalkyl,

(vi) aryl selected from the group consisting of phenyl and napthyl, or

(vii) heteroaryl selected from the group consisting of pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, tetrazolyl, furanyl, imidazolyl, triazinyl, pyranyl, thiazolyl, thiophenyl, triazolyl, oxazolyl, isoxazolyl, thiazolyl, oxadiazolyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzofuranyl, and benzoxazolyl,

wherein said alkyl, cycloalkyl, aryl or heteroaryl is unsubstituted or substituted with one or more

(A) halo,

(B) —OH,

(C) —CN,

(D) —O—C 1-10 alkyl,

(E) —C 3-12 cycloalkyl, or

(F) aryl selected from the group consisting of phenyl and napthyl;

R 3 is

wherein R 5 is C 1-10 alkyl, wherein said alkyl is unsubstituted or substituted with one or more halogen;

R 6a , R 6b , and R 6c are independently selected from the group consisting of:

(1) hydrogen,

(2) halo,

(3) —C 1-10 alkyl,

(4) —OH,

(5) —CN,

(6) —C 3-12 cycloalkyl, and

(7) —O—C 1-10 alkyl;

R 20 is selected from the group consisting of

(1) hydrogen, and

(2) C 1-10 alkyl;

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

2. A compound of claim 1 wherein R 1 is phenyl and Q 1 is CH 2 .

3. A compound of claim 1 wherein Y is NH 2 .

4. A compound of claim 1 wherein A is unsubstituted C 1-6 alkyl.

5. A compound of claim 1 which is a compound of formula (II)

and pharmaceutically acceptable salts thereof, and enantiomers and diastereomers thereof, wherein A, Q 1 , X, Y, R 1 and R 2 are as defined in claim 1 , and R 14 is selected from the group consisting of:

(1) hydrogen,

(2) halogen, and

(3) C 1-10 alkyl.

6. A compound of claim 5 wherein R 14 is halogen.

7. A compound of claim 5 wherein R 1 is phenyl and Q 1 is CH 2 .

8. A compound of claim 1 which is a compound of formula (III)

and pharmaceutically acceptable salts thereof, and enantiomers and diastereomers thereof, wherein A, Q 1 , X, Y, R 1 , R 2 , R 6a , R 6b and R 6c are defined in claim 1 .

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

10. A method for treating Alzheimer's disease in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

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

or a pharmaceutically acceptable salt thereof.