Compounds for treatment of Alzheimer's disease

1. A compound of the formula (III)

or a pharmaceutically acceptable salt thereof; wherein

a is optionally substituted methylene or C(O), and b is O, S(O), S(O) 2 , or NR 6 ;

Q 1 is a divalent carbocycle, heterocycle, unsaturated heterocycle, aryl, or heteroaryl, each of which is optionally substituted;

X 2 is NR 1 , C(O), S(O), S(O) 2 , NR 1 —C(O), NR 1 —S(O), NR 1 —S(O) 2 , optionally substituted alkylene, or optionally substituted alkylenoxy;

X 3 is C(O), S(O), S(O) 2 or CHR 1 ;

R is heteroaryl, aryl, heteroarylalkyl or arylalkyl, each of which is optionally substituted;

X 1 is optionally substituted alkylene;

A is O or NR 1 ; or A is a nitrogen atom, and A and X 1 are taken together to form an optionally substituted heterocycle;

R 1 is independently selected in each instance from hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, or heteroarylalkyl, each of which is optionally substituted;

R 2 , R 3 , and R 4 are in each instance hydrogen;

R 5 is alkyl, alkenyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, or heteroarylalkyl, each of which is optionally substituted;

R 6 is hydrogen, OR 7 , S(O)R 7 , S(O) 2 R 7 , C(O)R 8 , C(O)OR 7 , C(O)NR 9 R 10 , S(O)NR 9 R 10 , S(O) 2 NR 9 R 10 , alkyl, alkenyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, or heteroarylalkyl, each of which is optionally substituted;

R 7 is in each instance independently selected from the group consisting of alkyl, alkenyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which is optionally substituted;

R 8 is in each instance independently selected from hydrogen, or selected from the group consisting of alkyl, alkenyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which is optionally substituted;

R 9 and R 10 are in each instance independently selected from hydrogen, or selected from the group consisting of alkyl, alkenyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, alkylsulfonyl, arylsulfonyl, and heteroarylalkyl, each of which is optionally substituted; or R 9 and R 10 and the attached nitrogen form an optionally substituted heterocycle; and

R 11 is hydrogen, or R 11 is alkyl, alkenyl, heteroalkyl, alkoxyl, thioalkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, or heteroarylalkyl, each of which is optionally substituted.

2. The compound of claim 1 wherein a is C(O), b is NR 6 , and R 6 is arylalkyl or alkyl.

3. The compound of claim 1 of formula (IIIa) or formula (IIIb)

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 of formula (IIIc)

or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 of formula (IIIf)

or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition where the pharmaceutical composition includes one or more compounds of claim 1 .

7. The compound of claim 1 of formula (IIId) or formula (IIIe)

or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 wherein R 6 is optionally substituted benzyl.

9. The compound of claim 1 wherein R 6 is optionally substituted benzyl, and R 11 is H.

10. The compound of claim 1 wherein R 6 is optionally substituted benzyl, and R 11 is alkyl.

11. The compound of claim 1 wherein R 6 is optionally substituted alkyl, and R 11 is H.

12. The compound of claim 1 wherein R 6 is optionally substituted alkyl, and R 11 is alkyl.

13. The compound of claim 1 wherein R 6 is optionally substituted branched alkyl, and R 11 is H.

14. The compound of claim 1 wherein Q 1 is 1,3-phenylene, optionally substituted with from 1 to 3 substituents selected from hydroxy, halo, alkoxy, C(O)-alkyl, C(O)-aryl, C(O)-alkoxy, C(O)-amino, S(O)-alkyl, S(O) 2 -alkyl, S(O)-aryl, S(O) 2 -aryl, alkyl, heteroalkyl, cycloalkyl, alkenyl, amino, alkylene-amino, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which is optionally substituted.

15. The compound of claim 1 wherein X 2 -Q 1 -X 3 is selected from the formulae

16. The compound of claim 1 wherein Q 1 is divalent phenyl optionally substituted with a heteroaryl, selected from the group consisting of pyrrolyl, furanyl, thienyl, pyrazolyl, imidazlyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, and pyrazinyl, each of which is optionally substituted.

17. The compound of claim 1 wherein Q 1 is divalent phenyl optionally substituted with a heterocyclyl selected from the group of tetrahydrofuranyl, bistetrahydrofuranyl, tetrahydropyranyl, morpholinyl, piperdinyl, and piperazinyl, each of which is optionally substituted.

18. The compound of claim 1 wherein X 2 is C(O).

19. The compound of claim 1 wherein R 5 is optionally substituted benzyl.

20. The compound of claim 1 wherein A is a nitrogen atom, and A and X 1 are taken together to form an optionally substituted heterocycle.

21. The compound of claim 1 wherein A is NH or N-alkyl, and X 1 —R are taken together to form

wherein Y 2 and R a are each independently selected from alkyl or heteroalkyl, each of which is optionally substituted.

22. The compound of claim 1 wherein A is NH or N-alkyl, and X 1 —R are taken together to form a radical of the formula

wherein X is NR 1 , O, or S; and Y 2 and R a are each independently selected from H, or alkyl, haloalkyl, aminoalkyl, or heteroalkyl, each of which is optionally substituted.

23. The compound of claim 1 wherein R—X 1 -A-X 2 are taken together to form a radical of the formula:

wherein X is O or S; Y 2 is hydrogen or halogen, or is alkyl, halo alkyl and heteroalkyl, each of which is optionally substituted.