Benzylether and benzylamino beta-secretase inhibitors for the treatment of alzheimer's disease

1. A compound of formula (I):

wherein:

X is O or NH;

Y is CH;

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,

(c) —C 2-6 alkenyl,

(d) —C 2-6 alkynyl,

(e) —OH,

(f) —CN, or

R 2 is selected from the group consisting of:

(1) R 4 —S(O) 2 N(R 7 )—, wherein R 4 is C 1-6 alkyl, wherein said alkyl is unsubstituted or substituted with one or more

(a) halo,

(b) —C 1-6 alkyl,

(c) —OH,

(d) —CN, or

(e) —O—C 1-6 alkyl; and

R 7 is selected from the group consisting of

(a) hydrogen, and

(b) —C 1-6 alkyl,

wherein said alkyl is unsubstituted or substituted with one or more

(i) halo,

(ii) —C 1-6 alkyl,

(iii) OH,

(iv) —CN, or

(v) —O—C 1-6 alkyl;

R 3 is selected from the group consisting of:

wherein R 5 is C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl;

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

(1) hydrogen,

(2) halo,

(3) —C 1-6 alkyl,

(4) —C 2-6 alkenyl,

(5) —C 2-6 alkynyl,

(6) —OH,

(7) —CN, and

(8) —O—C 1-6 alkyl;

R 9 and R 10 are independently selected from the group consisting of:

(1) hydrogen, and

(2) C 1-6 alkyl,

(3) —C 2-6 alkenyl, and

(4) —C 2-6 alkynyl,

or R 9 and R 10 are joined together with the nitrogen atom to which they are attached to form a pyrrolidine ring, which is optionally substituted with

(a) C 1-6 alkyl,

(b) —C 2-6 alkenyl,

(c) —C 2-6 alkynyl,

(d) (CH 2 ) n -phenyl, and

(e) (CH 2 ) n -furanyl;

wherein said alkyl, phenyl and furanyl are unsubstituted or substituted with one or more

i) halo,

ii) —C 1-6 alkyl,

iii) —OH,

iv) —CN, or

v) —O—C 1-6 alkyl; and

R 11 is selected from the group consisting of

(1) —CH—,

(2) —O—, and

(3) NH—,

provided that when R 11 is —CH— the dotted line forms a bond and when R 11 is —O— or —NH— the dotted line is absent;

R 12 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl;

m is 1 or 2;

n is 0, 1, 2, 3 or 4;

p is 1, 2, 3 or 4;

and pharmaceutically acceptable salts thereof.

2. The compound of claim 1 , wherein m is 1 and R 1 is phenyl unsubstituted or substituted with one or more chloro or fluoro.

3. The compound of claim 1 , wherein m is 2 and R 1 is phenyl unsubstituted or substituted with one or more chloro or fluoro.

4. The compound of claim 1 , wherein R 2 is (R 4 )—S(O) 2 N(R 7 )— and R 7 is C 1-6 alkyl.

5. The compound of claim 4 wherein R 4 and R 7 are each methyl.

6. The compound of claim 1 , wherein R 2 is

7. The compound of claim 1 wherein R 3 is

8. The compound of claim 7 wherein R 5 is methyl.

9. The compound of claim 1 wherein R 3 is

and R 9 and R 10 are joined together with the nitrogen atom to which they are attached to form a pyrrolidine ring which is unsubstituted or substituted with

(a) C 1-6 alkyl,

(b) (CH 2 ) n -phenyl, or

(c) (CH 2 ) n -furanyl.

10. The compound of claim 9 wherein R 9 and R 10 are joined together with the nitrogen atom to which they are attached to form a pyrrolidine ring which is substituted with —(CH 2 ) n -furanyl wherein n is 0.

11. The compound of claim 10 , wherein R 3 is

12. The compound of claim 1 wherein R 3 is

13. The compound of claim 1 of formula II:

wherein x, Y, R 1 , R 2 , R 5 , R 6a , R 6b , R 6c and mare as defined in claim 1 .

14. The compound of claim 1 of formula (III):

wherein X, Y, R 1 , R 2 , R 9 , R 10 and m are as defined in claim 1 .

15. The compound of claim 1 of formula (IV):

wherein X, Y, R 1 , R 2 , R 11 , R 12 and mare as defined in claim 1 .

16. The compound of claim 1 which is selected from the group consisting of:

and pharmaceutically acceptable salts thereof.

17. A pharmaceutical composition comprising an effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.